This study attempts to identify the specific role that each of three conditions afflicting homeless, mentally ill, chemically misusing (HMICM) men plays in exposing these men to the risk of HIV infection. Three hundred and fifteen HMICM men (33 of whom were HIV+) were interviewed on intravenous drug use (IVDU) and sex practices. Two scales of risky IVDU practices and sex conducts were constructed and analyzed in relation to HIV status. The severity of homelessness, mental illness, and chemical misuse, then, were analyzed as possible predictors of risky IVDU and sex practices. Strong correlations were found between IVDU practices and HIV seropositivity, and between risky sex conduct and HIV seropositivity. Serious depression was the strongest predictor of risky IVDU practices. Prolonged homelessness was the condition most associated with risky sexual conduct. This study concludes that HMICM men are at high risk for HIV infection, stemming, predominately, from two conditions: depression, leading to risky IVDU practices, and homelessness, leading to risky sex conduct with two separate types of risky behavior.