Results obtained in vitro suggest that mycoplasmas act as cofactors with the human immunodeficiency virus (HIV) in the development of AIDS. Mycoplasmas, including Mycoplasma fermentans, Mycoplasma pirum, and Mycoplasma penetrans have since been isolated from HIV-infected individuals. In addition, M. fermentans has been detected by different investigators in numerous tissues and in the blood of HIV-infected patients. Higher titers of antibodies to M. penetrans have also been found in HIV-infected patients as compared with noninfected individuals. These mycoplasmas have been shown to have the capacity to invade cells and to be potent immunomodulators. Although there is no doubt that mycoplasmas are found in HIV-infected individuals and eventually produce systemic infections, their pathogenic role in association with HIV remains to be determined.