We report on two patients with acute human immunodeficiency virus (HIV) infection, who developed an infectious mononucleosis-like clinical episode with thrombocytopenia and granulocytopenia. In both cases we detected the presence of IgG antigranulocyte antibodies and in one case the presence of IgG, IgM and IgA antiplatelet antibodies. The mechanisms of these cytopenias are discussed. The association between such autoimmune cytopenias and acute HIV infection has not been previously reported. We suggest testing for HIV seroconversion in patients with a seronegative infectious mononucleosis-like syndrome belonging to groups with a high risk for HIV infection.