In Chapters 5 and 6 of The Crying of Lot 49, Oedipa becomes increasingly isolated from her friends and family. Mucho is lost to LSD, Dr. Hilarius goes mad, and Metzger elopes, and Driblette commits suicide, to name a few specific instances. Oedipa’s world, both the “real” domain as well as the one concerning Tristero and Thurn and Taxi, is spiraling out of control. This growing feeling of isolation is hinted earlier on at the beginning of Chapter 5 when the narrator observes, “Oedipa sat, feeling as alone as she ever had, now the only woman, she saw, in a room full of drunken male homosexuals…Despair came over her, as it will when nobody around has any sexual relevance to you” (94). In a scene reminiscent of T. S. Eliot’s “The Wasteland,” parallels can be drawn between Oedipa and the typist, especially with relation to the young man carbuncular in an automatic, emotionally empty sexual encounter in “The Fire Sermon.” The level of dissonance in Pynchon’s amalgamation of multiple cultural,  geographical, and chronological spaces also relates closely with the cacophonous melding that erupts in The Waste Land.

The sheer lack of communication and genuine human interaction between characters, further worsened by the protagonist’s growing retreat into herself and conspiracy theories, also cuts ties between the reader and the world of The Crying of Lot 49. Oedipa is the main lens through which readers can explore the novel’s fictional world, and this lens becomes increasingly clouded or fractured as Oedipa cuts her ties, either intentionally or not, to this world. The third person limited point of view also contributes to this growing sense of loss and isolation on both the part of Oedipa and the reader. Even as Oedipa learns more about Tristero, only more questions follow, and as she begins to doubt whether her entire voyage might be a foolish wild-goose chase orchestrated by Pierce and becomes suspicious of the acquaintances that are still alive and relatively sane, the reader faces a repeating dilemma of who to trust as options exponentially narrow as the novel races towards an inconclusive end.