Patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related conditions are known to have abnormalities of T cell subpopulations, including a decreased helper/inducer (bearing the CD4 antigen) to suppressor/cytotoxic (bearing the CD8 antigen) T cell ratio and decreased absolute numbers of T cells with the CD4+ phenotype. Infection of T cells with a retrovirus, termed human immunodeficiency virus (HIV), is thought to be important in these abnormalities. HIV infection alone does not adequately explain the CD4+ T-cell abnormalities seen in AIDS, however, and the nature of T-cell destruction in this disease remains poorly characterized. Here we describe an AIDS-related serum autoantibody that reacts with an antigen of relative molecular mass 18,000 (Mr 18K) restricted to lectin-stimulated or HIV-infected CD4+ T cells. The antibody also suppresses proliferation of CD4+ T cells in vitro and induces cytotoxicity of these cells in the presence of complement. Its role in the development of AIDS merits attention.