The human immunodeficiency virus (HIV) seroprevalence among a selected sample of 169 high-risk homeless men residing in a congregate shelter in New York City, NY, was 62%. Seropositivity for HIV correlated significantly with intravenous drug use (odds ratio, 3.3; 95% confidence interval, 1.4 to 4.4) and active tuberculosis (odds ratio, 7.0; 95% confidence interval, 3.4 to 13.5). Most cases of active tuberculosis were among homeless men with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex; and significant CD4 lymphocyte depletion was associated with active tuberculosis. Total time homeless correlated positively with active and latent tuberculosis infection. Compliance rates with return for HIV antibody test results, medications, and follow-up visits were 70%, suggesting a significant degree of knowledge, awareness, and personal concern regarding HIV infection among homeless men; yet 28% of homeless intravenous drug users continue active drug injection, despite HIV infection. Cohabitation in overcrowded congregate dormitories creates a risk of airborne transmission of tuberculosis, which is a common reactivation infection in HIV-seropositive homeless men. Medically appropriate housing should be provided to such homeless persons, and expanded HIV antibody testing, counseling, and medical services on site should be offered to residents of shelters.