Pitt and Jolie, with children in tow, were in Venice to talk about his film on Western outlaw Jesse James. The movie is competing for the top Golden Lion award at the city's film festival.
Pitt and Jolie already have four children including a 15-month-old girl, Shiloh, born to the couple. Jolie has also adopted three children close in age from Cambodia, Ethiopia and Vietnam.
Asked by Italian state TV whether they were ready for a fifth, Pitt replied: "Yeah we're ready."
He did not indicate whether they planned another biological child or if they would adopt.
Earlier on Sunday, Pitt told a news conference fatherhood was fun and good for his work, though he's not getting much sleep.
"It's the most fun I've ever had and also the biggest pain ... I've ever experienced," he said when asked what it was like to become a family with four children in a short space of time. "I love it and can't recommend it any more highly — although sleep is nonexistent."
Having four small children "makes me much more efficient because when I work, I really have to focus. I know I've less time to get things done. Actually, I'm quite pleased by it," said Pitt.
"The Assassination of Jesse James by the Coward Robert Ford," stars Pitt, Casey Affleck and Sam Shepherd, and was directed by Andrew Dominik. Pitt described it as "more a gangster film than a Western."
Pitt plays James in the last year of his life as he lapses into paranoia over potential betrayal by accomplices and intimates.