The presence of platelet- and neutrophil-bound immunoglobulin (PBIg and NBIg) in thrombocytopenic or neutropenic HIV-infected individuals has led to the concept that in HIV infection thrombocytopenia and neutropenia are mediated by autoimmunity. However, PBIg and NBIg were also demonstrated in non-cytopenic HIV-infected individuals. We determined the prevalence of autoantibodies against neutrophils and platelets by immunofluorescence in randomly chosen persons in different stages of asymptomatic and symptomatic HIV infection. Platelet and neutrophil autoantibodies already appeared in the asymptomatic stage and their prevalence further increased in the symptomatic stages. No correlation was found between the presence of either platelet or neutrophil antibodies and the occurrence of circulating immune complexes in the blood or the serum immunoglobulin level. There was no significant difference in neutrophil counts in HIV-infected persons with or without neutrophil autoantibodies. In addition, no significant difference in neutrophil count was found between HIV-infected and non-HIV-infected persons. HIV-infected individuals with platelet autoantibodies tended to have a lower platelet count than HIV-infected individuals without these antibodies. However, the platelet count in HIV-infected individuals without platelet antibodies was significantly lower than in the non-HIV infected persons. Thus, autoantibodies against platelets and neutrophils occur early in HIV infection and their prevalence is correlated with disease progression. Their presence is associated with cytopenia only in a limited number of persons. Non-immune mechanisms also mediate thrombocytopenia in HIV infection.