Numerous studies in developed countries have revealed a higher prevalence of antibodies to Mycoplasma penetrans in homosexuals infected with HIV than in other HIV-positive and HIV-negative population groups. To confirm whether this association prevails in African countries, a cross-sectional analysis was conducted in Brazzaville, Congo, in 1993-94. Tested were 116 HIV-negative blood donors and 149 HIV-infected hospital patients. The prevalence of antibodies to M. penetrans was 13.4% in the HIV-positive and 15.5% in the HIV-negative group. Among HIV-infected patients, M. penetrans seropositivity was more frequent among patients under 30 years of age, those with CD4 lymphocyte counts below 200 cells/cu. mm, and those with CD4 lymphocyte percentages below 5%. This correlation between the prevalence of antibodies to M. penetrans and the severity of immunosuppression has been documented in studies from France and the US as well. The high prevalence of antibodies to M. penetrans in the late stages of HIV infection in Western homosexuals and Congolese heterosexuals may reflect a cohort effect in which the groups most exposed to HIV at the beginning of the epidemic were also those most exposed to M. penetrans infection. It is also possible that the development of M. penetrans is due to immunosuppression or, alternatively, infection influences HIV multiplication.