As Anne Hathaway tells Jake Gyllenhaal in “Love & Other Drugs” after he rebounds from a thrashing with an invite for coffee: “Oh, you’re good.” And he is.

When the actor gets on the phone from New York at nearly 6 p.m. on a recent Saturday he reveals, “I just want you to know you’re the last interview of the day. We saved the best for last.”

If he’s exhausted from answering the same half-dozen questions on a loop for the past eight hours, he doesn’t betray it. Besides, who else would inquire about the ink?

Asked about the fake Steelers tattoo he unveiled on “Jimmy Kimmel Live” in December, he says, “You know my devotion then. You know my deep devotion to Pittsburgh.”

As for that team logo on his lower back, he playfully asks, “What do you mean? That’s a real tattoo,” but of course it will be covered up in any future movies. And then he lets the cheeky ruse drop and volunteers, “I really legitimately had a wonderful time when I was in Pittsburgh.”

Pressed about some favorite haunts, he says, “Oh, gosh. Let’s see, I went to so many places. I like to eat. I ate my way around. I ate everywhere. I wish I could remember the names of everything.”

Without any prompting, he recalls, “I loved Dish — the restaurant Dish. I did love the pancakes at Pamela’s, I’d have to say, which is probably the go-to. 21st Street Coffee. There was a Greek place that was right where I lived [in Squirrel Hill], I don’t remember the name.”

Mr. Gyllenhaal, who shot the Ed Zwick film from mid-September to late November 2009, says, “I was surprised at how much I loved all the food and actually how much I loved Pittsburgh. … I loved the change of seasons there, and I loved the people there and I had a great time. I would love to make another movie in Pittsburgh.”

“Love & Other Drugs” is based on the nonfiction book “Hard Sell: The Evolution of a Viagra Salesman” by Jamie Reidy, who documented his experience as a Pfizer salesman.

On screen, he’s now called Jamie Randall, and while he’s still peddling Pfizer pills and charming everyone in his ZIP code, he also embarks on a lusty relationship with Ms. Hathaway’s Maggie, a spirited but ailing artist.

Mr. Gyllenhaal spent a day and a half cumulatively with Mr. Reidy, who also visited the set. “A few hours here, a few hours there, interviewing him and stealing his stories and stealing his rhythms and his voice and stealing his personality a little bit.”

Not to mention taking note of his “almost unbridled confidence,” all evident in the movie opening in theaters Wednesday.

Behind the scenes, at least at the start, Mr. Gyllenhaal gets the jitters like anyone starting a new job. “I hardly ever sleep the first night before shooting. It’s like, I never believe I’m making a movie. I think I’m going to forget all the things I’ve rehearsed and prepared.”

The film opens in 1996 and covers the period later in the decade when Pfizer pharmaceutical reps tried to sweet talk their way into doctors’ offices — and drug cabinets and onto their prescription pads — with such products as Zoloft, Zithromax and Viagra.

“I think my opinion of the pharmaceutical world has changed a bit, only because I think I never was able to see it as sales. I always naively thought it was only about people’s health, and I know a lot of people would argue that that’s what it is, but ultimately, it’s a billion-dollar industry and it’s about money and making money.

“And I learned a lot, that it’s in the hands of some very responsible people and some very irresponsible people and so, yeah, I asked certain people a lot of questions about things and whether they would take the drugs they sell and some people said no.”

Even today, doing research into pharmaceutical sales is a little like trying to pull the curtain back at the CIA, says the actor who portrayed a CIA analyst in “Rendition.” He may be best known, however, for his Oscar-nominated turn as a lovesick rodeo cowboy in “Brokeback Mountain,” but he has a rich roster of roles.

Among them: the buff, long-haired lead in “Prince of Persia: The Sands of Time”; an editorial cartoonist obsessed with a serial killer in “Zodiac”; an enlistee who finds himself in the first Gulf War in “Jarhead”; and a brilliant but problematic teen in “Donnie Darko.”

He and Ms. Hathaway, who played his unhappy wife in “Brokeback,” had stayed in touch since co-starring in the haunting 2005 release.

“We weren’t friends like we are now. … We shared a great bond from that movie; everybody involved in it did.” The tragic romance also starred the late Heath Ledger along with Michelle Williams.

Shedding inhibitions

“Love & Other Drugs,” rated R, required the leads to shed clothes and inhibitions for intimate moments.

“I think it’s just my job. Ultimately you can’t be the guy who’s like, ‘I feel really uncomfortable here. I don’t want to do it,’ when you’re the one who chose it. You have protection in your character.”

The 29-year-old actor is not getting naked as much as Jamie Randall is. “It’s not me. I feel like I’m in a character.

“It’s just inevitably uncomfortable, sitting there partially naked or feigning sex in front of 50 people, but we’re all there to do a job. And Ed hired some of the best people in the business to do their jobs. So I trusted people, and I knew that they were all respectful, and you just kinda got to go with God on that.”

The cast also counts Josh Gad as Jamie’s brother; George Segal and the late Jill Clayburgh as their parents; Oliver Platt as the drug rep showing Jamie the ropes; Hank Azaria as a physician; Gabriel Macht as a rival salesman; and Judy Greer as a doctor’s office receptionist.

“Love & Other Drugs” defies easy categorization. It’s not a traditional romcom or a straight drama or faithful adaptation of a memoir.

Ms. Hathaway’s character has early-onset Parkinson’s disease and a funny, moving and bracing scene has her listening to other patients and Jamie getting some unsolicited advice from a spouse.

“I think it has its own voice, that’s for sure. I think it incorporates the new kind of comedy that’s become popular in the past little while and it’s also emotional. We like to call it an ’emotional comedy,’ ” Mr. Gyllenhaal says.

‘The stakes are high’

“It’s about real things and the stakes are high, and it’s not just a romantic comedy about, like, is the guy going to get the girl and the girl going to get the guy. Are these two people actually, legitimately ready for what’s ahead of them — which is life and all the things that get thrown at you in a lot of ways.”

It may be a progressive illness here, but most couples will find their love tested by the inevitability of decline and, ultimately, death. “It happens and it’s kind of an interesting thing to make something that’s a romance about that.”

When Mr. Gyllenhaal was in town, trips to the supermarket would invariably inspire fellow shoppers to pull out their cell phones in the middle of the produce aisles and aim them in the same direction.

“I think we live in a world where people who are in the public eye have to know that what they do is going to be documented. There is definitely an ability for privacy, but most of the time, you just have to accept that that’s what it is.

“And I think you have to be who you are and do what you love, and I think most of the time, people are pretty respectful and when they’re not, they’re not.”

He says he loves his fans and making movies and the attention that comes with it.

When it’s suggested that 99 percent of the population can run out for coffee or stop for gas without checking in the mirror, he says, “So can I. It just depends on what you believe. If you want everybody to see you looking a certain way, then if that makes your life happy, then that’s great. That would make me miserable. If you’re aware of it all the time, I think you’re not living.

“People are going to make mistakes, they’re going to have amazing times, hard times, just like everybody, and people might document that and say whatever they’re going to say, but ultimately it’s just life. You can take a picture of it or not, but you gotta live it.”

And, as it turns out, “Love & Other Drugs” is one of the last movies Ms. Clayburgh shot. She died earlier this month at age 66 of leukemia.

“She was really an extraordinary person,” Mr. Gyllenhaal says, with a life far shorter than she deserved. “It’s clear from having been sick that she really cherished her time, and it’s clear because over two days of working with her, she made a lasting impression on me for the rest of my life.”

Mr. Gyllenhaal added that he deeply cared about her and thought she was incredible. “It’s hard to make someone feel about you if you don’t have something incredibly special and she definitely did.”