The in vivo and in vitro synthesis of anti-tetanus toxoid antibody (anti-tet) was measured after booster immunization with tetanus toxoid in 9 patients with systemic lupus erythematosus (SLE) and 9 controls. In vitro culture of peripheral blood lymphocytes (PBL) from both patients and controls showed maximal anti-tet synthesis 7 days after booster immunization, and maximal serum titers occurred by day 14. The initial in vitro burst of anti-tet synthesis was not dependent upon pokeweed mitogen (PWM) stimulation, whereas later synthesis was PWM dependent. Two differences between patients and controls were observed: 1) patients with SLE had a lower mean pre-boost serum titer of anti-tet, and 2) one-third of the patients showed a blunted serum anti-tet response. To study whether these abnormalities were a result of altered immune regulation, anti-tet synthesis was measured by the coculture of separated SLE-B or control-B cells and separated SLE-T or control-T cell populations (+/- irradiation to remove suppressor T cell activity). These coculture studies showed that both abnormalities were due to a lack of SLE-B cell response, not to abnormalities of SLE-helper T or SLE-suppressor T cell function.