In their latest project, Jake Gyllenhaal and Anne Hathaway embrace their right to bare arms. And legs. And shoulders. And backs. And, um, assorted other body parts.

The Brokeback Mountain stars team again for Love & Other Drugs, one of director Edward Zwick’s rare big-screen forays into the world of relationships and romance that date to 1986’s About Last Night with Rob Lowe and Demi Moore.

The 58-year-old producer/director has also explored these themes as the creator of the TV shows thirtysomething (1987-91) and Once and Again (1999-2002).

In Zwick’s new dramedy, opening Wednesday, Gyllenhaal, 29, plays Jamie Randall, a slick pharmaceutical salesman peddling the likes of Zoloft and Viagra, who spurns his womanizing ways when he falls for Maggie (Hathaway), a young artist with early-onset Parkinson’s as well as major commitment issues.

“It was an intimate movie, obviously, and one that really depended on getting to know each other,” Zwick says. However, the two performers came in with a connection both personal and professional.

Gyllenhaal and Hathaway worked only eight days together on 2005’s Brokeback Mountain, which cast the two performers as a married couple, but they had the luxury of a long rehearsal period to perfect some of the key sequences with Zwick, from the heartfelt finale to Jamie’s first panic-inducing moment of saying “I love you” to Maggie.

“The first thing (Zwick) said to me was, ‘I’ve seen you be vulnerable in movies, but can you not be vulnerable?’ I was like, ‘Yeah! I can not be vulnerable!’ That was a big thing,” Gyllenhaal says. “Real actors respond to someone saying, ‘Trust your instinct.’ ”

Avoiding cliché was key for Hathaway, 28. “We were sitting there doing the scene, and we just started to improv. I was asking him if he was OK and if he wanted a glass of water and he did, and I tried to rub his shoulders and that’s when he’s like, ‘Don’t touch me!’ And I was like, ‘All right!’ And that made it into the movie, his reaction and my yelp and the whole thing.”

There was also a lot of collaboration in the film’s frequent love scenes and sequences with the two stars in various states of partial and total undress. Gyllenhaal admits Love & Other Drugs is definitely a racy film, but in a different way from Brokeback Mountain, which featured an on-screen romance between him and Heath Ledger.

“It’s sexy, but in a really good way,” Gyllenhaal says. “When two people are in love, they’re comfortable with each other — naked physically, literally and figuratively — and we wanted to portray that.”

Hathaway says that figuring out how they were going to do “this nudity thing” was one of the first conversations they had with Zwick. “We’ve pretty much seen each other partially naked before. It removed any kind of shyness and modesty about it. It made it very practical, like, ‘Oh, we’ve done this!’ There are no surprises there, nothing to be embarrassed about, so I think we were able to launch into it with confidence.”

Mapping Jamie and Maggie’s sexual relationship was a particularly big part of the movie as they became closer and more intimate, according to Gyllenhaal. “The sex they literally have is primal, the positions and everything. That’s Annie’s idea.”

He laughs. “It’s funny that I never think about these things. When you make a movie, it’s just this thing you’re doing among a very small group of people, and then you’re talking to people about how you were naked.”

Hathaway says that Gyllenhaal went out of his way to make sure she always felt comfortable on the set. “He’s a very strong person, so he likes to give a lot to people, and sometimes I do worry about him giving too much.

“I want to say, ‘I’m good, dude. Take care of yourself. Don’t worry about it.’ That protective instinct is really, really strong within him.”

Zwick sees a competitive streak between them, but in the very best way. “They’re both determined to bring their best game to every scene and every moment. They push each other to do the same,” he says.

Gyllenhaal, however, finds the secret of their chemistry in the sense of shared rhythm between himself and Hathaway. “We’re both incredibly musical, so all the rhythms in the movie — be they comedic, dramatic, sexual, whatever — we really feed off of each other really well,” he says.

“I don’t think another two people could have had the same thing, or me with someone else or her with someone else. We have something very special, I think, and I cherish that.”