The first part of this novel presents a detailed picture of the Jewish Californian Cooper family, centering on the sixty-year-old Louise, who is dying of breast cancer. Her husband, Nat, is unfaithful, and, she suspects, only loves her when she is at her weakest and most sick. Her daughter, April, is a lesbian folk singer who becomes pregnant with the help of a gay male friend and a turkey baster. Danny, the son, is also gay, living in New York with Walter, his lover, who is becoming increasingly detached and obsessed with internet sex groups.

Louise considers herself lucky, though, compared with her younger sister Eleanor, partially disabled by childhood polio, disorganized and ill-groomed and married to Sid, whom Louise finds deeply unattractive. Eleanor's son is a sociopathic drug addict, and her daughter has ovarian cancer caused by Eleanor's taking DES (diethylstilbesterol) in pregnancy. She sends Louise newspaper cuttings about the causes of homosexuality and the dangers of AIDS.

The first part having established the complex dynamics and histories of the family's relationships, the second brings the entire family together in the crisis of Louise's final illness and death (a reaction to chemotherapy drugs causes severe chemical burns and she dies in a burn unit in a San Francisco hospital). After her death, the new dynamics of the family are established, and Louise's son and daughter conclude that their mother had "a terrible life" (p. 261).

The short third part shows that no such conclusion is possible, that even those closest to us remain terribly but fascinatingly unknowable. A flashback to a point just before Louise's final illness describes her attempt to convert to Catholicism and a brief moment in which she experiences a marvelous sense of complete harmony.