Patients with the acquired immunodeficiency syndrome (AIDS) acquire undifferentiated B-cell lymphomas that are similar to African Burkitt's lymphoma and contain Epstein-Barr virus (EBV). Using an in vitro assay system that measures a complex of cellular responses to EBV-infected lymphocytes, we found that B cells from 7 patients with AIDS and from 10 patients with AIDS-related disorders produced abnormally low numbers of immunoglobulin-secreting cells (P less than 0.001 as compared with normal controls) and that T-cell suppression, which was greater than 80 percent in EBV-seropositive normal controls, was absent. Instead, the patients' T cells markedly increased immunoglobulin production induced by EBV. In further studies, we determined that the mean frequency of circulating EBV-infected B cells capable of spontaneous outgrowth in vitro was 13 per 10(6) B cells in 7 patients with AIDS and 21 per 10(6) B cells in 10 patients with AIDS-related disorders--figures that were significantly higher than the mean in normal controls (P less than 0.001). Thus, patients with AIDS or AIDS-related disorders may be predisposed to the development of EBV-containing lymphomas, because they have a profound defect of T-cell immunity to EBV and abnormally high numbers of EBV-infected B cells in the circulation.