An investigation of 20 homosexual men with histologically confirmed Kaposi's sarcoma and 40 controls revealed significant associations between Kaposi's sarcoma and use of a number of drugs (amyl nitrite, ethyl chloride, cocaine, phencyclidine, methaqualone, and amphetamine), history of mononucleosis, and sexual activity in the year before onset of the disease. Patients with Kaposi's sarcoma also reported substantially higher rates of sexually transmitted infections than did controls. Multivariate analysis indicated independent significant associations for amyl nitrite and sexual activity and showed use of phencyclidine, methaqualone, and ethyl chloride to be non-significant. Evaluated at the median exposure for patients, the analysis yielded risk-ratio estimates of 12.3 for amyl nitrite (95% confidence limits 4.2, 35.8) and 2.0 for sexual activity (95% confidence limits 1.3, 3.1).