Successful Hollywood movie director Adam Kesher is facing problems in both his personal and professional life. His wife is openly cheating on him, she kicking him out of their house in the Hollywood hills. For his latest film, he is being threatened to cast the female lead with the actress of "their" choice, that actress who he will only know at the time she auditions, he facing unknown but severe consequences by the unknown forces backing her if he doesn't comply. Meanwhile, wide-eyed Betty Elms has just arrived in Hollywood from her home in Canada to begin an acting career, she staying at her Aunt Ruth's apartment while Aunt Ruth, who also works in the business, is away on a film shoot. Initially believing she a friend of Aunt Ruth's, Betty discovers a young woman in the apartment, she, calling herself Rita, suffering from amnesia and just taking refuge in the empty apartment in seeing Aunt Ruth leave. They come to the belief that Rita has suffered a concussion most likely from a vehicle accident that took place along nearby Mulholland Drive. From what they discover in Rita's purse which precludes them from involving anyone else least of all the police, Betty decides to help Rita discover who she really is. When Betty and Rita stumble across a dead body in following the leads, Adam, Betty and Rita's collective stories begin to merge and take on surreal qualities, however the direction of that surrealism arguably backward and not forward.