Bridesmaids star Melissa plays a foul-mouthed mother in the mid-life crisis comedy, directed by Leslie's husband Judd Apatow.
Leslie told Collider: " Melissa McCarthy was the hardest one to get through. That was impossible. I've never experienced that. Maybe one time, I'll crack up, and then I can hold it together, from then on. But with her, it was hours.
"We could not keep a straight face. Finally, we just gave up. Judd was using more than one camera, so we could just laugh. And the crew were all laughing. It was ridiculous. She's just the funniest person, ever."
Paul Rudd, who plays Leslie's husband in the movie, added: "I've seen people in tears before, but that was something otherworldly. People were leaving the room. Crew had to leave. It was impossible. And she just kept her composure through all of it."