The film, "State of Play," was to star Pitt as a political consultant-turned-journalist who helps investigate the death of a congressman's mistress.
He left the production Wednesday, Hollywood trade paper Daily Variety reported on its Web site.
"Brad Pitt has left the Universal Pictures production of 'State of Play,"' the studio said in a statement. "We remain committed to this project and to the filmmakers, cast members, crew and others who are also involved in making the movie. We reserve all rights in this matter."
A message left early Friday for Pitt's publicist, Cindy Guagenti, was not immediately returned.