Reiter's syndrome has been reported to occur in up to 10% of patients with HIV infection. However, no properly controlled epidemiological studies have been conducted to determine whether HIV infection is an independent risk factor or whether the immunodeficiency induced by HIV infection is permissive for infection with other arthritogenic organisms. The prevalence and incidence of Reiter's syndrome were determined in 1133 homosexual/bisexual men enrolled in the Johns Hopkins Multicenter AIDS Cohort Study. There was no difference in the prevalence of Reiter's syndrome at entry into the study in 1984 between 357 HIV-positive and 776 HIV-negative men: five per 1000 in both groups. During 5 years' follow-up, one case of Reiter's syndrome developed among each group of HIV-positive and HIV-negative men. These data fail to support a direct etiological role for HIV infection in the development of Reiter's syndrome.