B lymphocyte studies, in vivo and in vitro, were performed in 28 patients with systemic lupus erythematosus (SLE). After immunization with the primary test antigen haemocyanin, a decreased antigen specific humoral immune response was observed for all three Ig classes, irrespective of disease activity or the use of corticosteroids. Levels of antibodies against (recall) viral and nuclear antigens were increased during active disease. The in vitro spontaneous production of IgM and IgG, determined in the supernatant of 8 days cultures by ELISA, was highly increased in patients with active disease (reversely correlated with levels of complement C3, r = 0.74). Pokeweed mitogen-induced synthesis was decreased in all patients. The distribution of T cell subsets (OKT3, Leu 3a and OKT8 positive cells) was not different from controls, irrespective of disease activity. It is concluded that the primary humoral immune response is decreased in SLE, whereas a polyclonally activated B cell appears to be present. The normal T cell subset distribution does not support the primary role of the cell in the state of hyperactivity of the B cell.