WARNING: The following gives away everything about the plot of this movie and shold not be read before seeing the movie!!

The key to understanding the movie is realizing that the second part (everything after "Rita" opens the blue box) is "reality," and everything before that is Diane's dream, fantasy, or delusion of her life as "Betty." Betty is the likeable, good, talented, well-provided-for young actress who takes care of and is loved by Rita, as opposed to the vengeful, unsuccessful Diane who is the rejected lover of Camilla. Rita, of course, is the fantasy version of Camilla, who in real life was killed by Diane's hired hit man.

Betty's unreality is hinted at right from her initial appearance, where it turns out that the people who are being so extremely loving and adoring to her as they get off the plane are simply other passengers whom she has met en route. (These same adoring figures become hallucinated persecutors when her delusion later disintegrates.)

In the Betty fantasy, Diane is able to rescue and possess Rita, and to tell her that she loves her. In reality, Diane is so furious at her rejection by Camilla that she hires someone to kill her. At the beginning of the fantasy, Diane attempts to picture Camilla's death (in the botched hit in the limo at the very beginning of the movie) and then violent revolts against it, imagining instead that "Rita" escapes (but loses her memory and personality, thus erasing everything offensive to Diane). Rita, in the fantasy, ends up coming to Betty from the limo that stops on Mulholland Drive, as opposed to the reality of Camilla having Diane brought by limo to the house of Adam Kesher (the director) on Mulholland Drive, where Diane learns that Camilla and Adam are to be married. In the course of her fantasy, Diane manages to set it up that she is able to have Adam's marriage and career fall apart, have him beaten and punished, and have his choice to cast Camilla be foisted on him by gangsters, against his will. (She also manages to imagine, briefly, in the fantasy that it is she, Diane who should have gotten the role, were it not for a criminal conspiracy.) It is all a fantasy about how her life should have been. (In reality, we see how Diane got the idea of the name "Betty" from a waitress's name tag; whereas in the fantasy, Rita makes the connection to Diane's name in the same way.)

The announcement of the pivotal shift occurs in the bizarre Club Silencio, where the performances all insistently tell us that things are not as they appear: all is lip-synching, illusion and delusion. Betty begins to convulse uncontrollably, as her delusion begins to disintegrate. After this point, "the blue box" of memory is opened (using a blue key, based on the blue key the hit man leaves for Diane to inform her that Camilla has been killed), and the real story begins to be seen. What emerges is that Rita is a corpse lip-synching along to Diane's fantasy. Camilla is dead.

The collapse of the delusion leaves Diane persecuted by her own hallucinatory images, and ultimately leads to her suicide.

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