In a prologue set in 1976, American epidemiologist Don Francis arrives in a village on the banks of the Ebola River in Zaire and discovers many of the residents and the doctor working with them have died from a mysterious illness later identified as Ebola hemorrhagic fever. It is his first exposure to such an epidemic, and the images of the dead he helps cremate will haunt him when he later becomes involved with HIV/AIDS research at the Centers for Disease Control and Prevention.
In 1981, Francis becomes aware of a growing number of deaths from unexplained sources among gay men in Los Angeles, New York City and San Francisco, and is prompted to begin an in-depth investigation of the possible causes. Working with no money, limited space, and outdated equipment, he comes in contact with politicians, numerous members of the medical community (many of whom resent his involvement because of their personal agendas), and gay activists. Of the latter, some such as Bill Kraus support him, while others express resentment at what they see as unwanted interference in their lifestyles, especially in his attempts to close the local bathhouses. One day, when exercising at a local gym, Kraus notices a spot at the base of his leg, worrying that it might be Kaposi's sarcoma. After a series of blood tests, Kraus is horrified that his worst fears have been confirmed when he learns that he has been diagnosed with AIDS. While Francis pursues his theory that AIDS is caused by a sexually transmitted virus on the model of feline leukemia, he finds his efforts are stonewalled by the CDC, which is unwilling to prove the disease is transmitted through blood, and competing French and American scientists, particularly Dr. Robert Gallo. These medical researchers squabble about who should receive credit for discovering the virus. Meanwhile, the death toll climbs rapidly.