We studied the prevalence and risk factors for thrombocytopenia among 299 drug users and 461 homosexual men. The prevalence of thrombocytopenia was 3.3% in HIV-negative homosexual men, 8.7% in HIV-negative drug users, 16.4% in HIV-positive homosexual men, and 36.9% in HIV-positive drug users. With multivariate logistic regression HIV-seropositivity (odds ratio 3.3), a history of injecting drugs (OR 3.9), an increased number of lymphocytes (OR 0.44), an increased number of neutrophils (OR 0.53) and a larger mean platelet volume (OR 2.8) were independently and significantly associated with thrombocytopenia. The results obtained with linear regression analysis were consistent with the results of the logistic regression. The higher prevalence of thrombocytopenia among drug users was related to a history of intravenous drug use but not to recent injecting. The mechanisms causing thrombocytopenia among HIV-positives and HIV-negatives seem to be related, but HIV-infection seems to enhance thrombocytopenia in an independent way.