Isolated immune complexes from sera of 49 out of 67 human immunodeficiency virus-1-positive (HIV-1+) patients (CIC-HIV+), composed of anti-HIV-HIV-Ag, could induce apoptosis on normal phytohaemagglutinin (PHA)-activated lymphocytes. DNA degradation was detected by propidium iodide staining. This activity is directed against CD4+ lymphocytes as demonstrated by double binding of CIC-HIV+ and anti-CD4 on apoptosis cells. Expression of Fas antigen is prior to apoptotic phenomena. CIC-HIV+ apoptosis inducers belong mainly to asymptomatic HIV-infected patients, indicating that immune complexes from these patients can destroy CD4+ lymphocytes.