Cigarette smoking as a risk factor in progression of HIV-1 disease was investigated in the Multicenter AIDS Cohort Study of homosexual men. Longitudinal data for T-cell subsets, HIV-related clinical symptoms, smoking behavior, and AIDS medication use were collected semiannually from 2,499 HIV-1-seropositive men for up to 9 years. Survival methods, including Kaplan-Meier analysis and multivariate Cox regression models, were used to assess the effect of cigarette smoking on development of Pneumocystis carinii pneumonia (PCP), AIDS, death, and self-reported oral thrush. After adjustment for CD4+ lymphocyte count and use of antiretroviral and anti-PCP medications, smoking was not significantly associated with progression to PCP, AIDS, or death in either the HIV-seroprevalent or-seroincident cohort members. Among men who had baseline CD4+ cell counts > 200/microliter, smoking was associated with a 40% increase in the hazard of oral thrush (p < or = 0.01). These data indicate that cigarette smoking does not have a major effect on the progression of HIV-1 infection to AIDS or death but may affect the incidence of oral thrush.