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It is almost the year of the millennium, and Melissa meets her college friends Sarah and Doug and her first and only true love John for a reunion in Hyde Park. All four are in the midst of their careers. All struggle with the compromises that have marred their happiness. All wish to change the world, each in a different way. Sarah has left her government job for a new life as a yoga teacher. Doug is helping to birth a new value-based economy. John is a successful academic doctor. Melissa is ailing. They unite to turn John's success as a researcher to the cure of Melissa's mysterious chronic illness. What they find will change their lives and their imperiled world.

Colette, Melissa's childhood friend, abandons her marriage and home in Maine and flies to Melbourne. There she is taken in by her friend Reggie, who seems to know the secret of joy. Colette joins in the lives of striking individuals who lead her to view sexuality as a manifestation of the sacred. As she leaves behind the wounds caused by profane sexuality, she and her new friends clash with members of Reggie's family who force them to flee and to begin again.

Soon after Colette and her friends find a new home, an old boyfriend of Melissa's who is sojourning in Australia calls and expresses his desire to visit. Colette plans to use the visit as a chance to develop a job for herself; he plans to check up on Colette for Melissa. As they get to know each other, they see that despite differences in religion, origin, and experience, they are on very similar spiritual paths. When it is time for Randall to go home, Colette joins him in Chicago. When he becomes caught up in his old life, however, she returns to Australia to pursue her dream of giving birth to a sacred community.

It's the late 1980s, and Connie Martin, a doctor working for the Epidemiology Intelligence Service of the CDC, is called to Colorado to investigate an alarming outbreak of birth defects. Born illegitimate in the San Luis Valley as Consuela Martín, a name known only to close friends and to her beloved gamer and programmer husband, she arrives as an unknown. Joined by environmental activists who suspect the state's Superfund sites and by doctors and parents who fear for its children, Connie attempts to discover the link between habitat destruction and damage to innocents.

It's the early 1970s. Melissa and her friends begin their first year of college in the inner city of Chicago at a time when post-assassination riots, Great Society scholarship programs, and veterans returning from Vietnam create a sometimes explosive confluence of urban and rural, rich and poor, white and black, educated and uneducated. Coming of age in a violent, unjust, and yet hopeful time, they struggle to reconcile their hopes and opportunities with the shadows of war and the tragic limitations of colliding ideologies and ambitions.