San Francisco Police Lieutenant Frank Bullitt and his team are assigned by senator Walter Chalmers to protect mobster Johnny Ross for 40 hours. Ross is a Mafia informant who needs to testify and bring out evidence on a hearing on organized crime. However, two hitman kill Ross and shoot Bullitt's friend Stanton, and Bullitt is held responsible. He starts an investigation of his own to catch the killers, but Chalmers wants to stop him.