The course of disease associated with infection with the human immunodeficiency virus varies widely. Some patients deteriorate rapidly, while others live for years, even after an illness that defines the acquired immunodeficiency syndrome (AIDS). In this study, comorbidity, or the presence of concurrent health problems, was investigated prospectively as a possible co-factor for different rates of decline in 395 homosexual/bisexual men in the San Francisco Men's Health Study (SFMHS) who were infected with the human immunodeficiency virus (HIV). Comorbidity data obtained from baseline interviews included both chronic and infectious diseases as well as depression. Smoking, alcohol, and drug use were also examined. The most prevalent comorbid conditions were sexually transmitted diseases (90%) and hepatitis B infection (76%). Most chronic and acute concurrent health conditions were not significant discrete predictors of survival to AIDS or death after controlling for immune status and markers of disease progression. Significantly, other risk factors (e.g., depression and smoking) were found to be associated with more rapid progression. Men with symptoms of depression had a higher risk of progression of AIDS diagnosis; the relative hazard (RH) was 1.4 (95% confidence interval [CI], 1.00-2.08); smoking was associated with higher risk of death (RH, 1.6; 95% CI, 1.20-2.17). Older age was marginally associated with poorer survival to death. No associations were found between survival and alcohol and drug use.