Patients with rheumatoid arthritis and patients with lupus nephritis underwent total lymphoid irradiation (TLI). Peripheral blood mononuclear cells from these patients showed a decrease in pokeweed mitogen-induced immunoglobulin secretion after TLI. A defect in non-T cells contributed to the decreased response. No defect in the response of non-T cells to T cell-independent activators of B cells, Staphylococcus aureus Cowan 1 and Epstein-Barr virus, was observed after TLI. We conclude that TLI induces a selective deficit in B cells, which respond to T cell-dependent mitogen stimulation.