Unseparated mononuclear cells (10(5) cells/well) were cultured both in the presence and absence of pokeweed mitogen (PWM), and IgG secretion was measured by radioimmunoassay. In unstimulated cultures, levels of IgG secretion were found to be higher in a group of patients with multiple sclerosis (MS) than in control groups of healthy individuals or patients with other neurologic diseases (OND). By contrast, PWM-induced IgG secretion was similar in MS patients and in controls. In MS patients, levels of IgG secretion greater than 2500 ng/ml in unstimulated cultures were present in 29 (58%) of 50 patients with active disease and in only 3 (14%) of 21 patients with inactive MS (P less than 0.01; MS active vs inactive). Furthermore, levels of IgG secretion in unstimulated cultures were higher in patients who had abnormalities of circulating T-cell subsets consisting of reduced numbers of suppressor/cytotoxic (T8) cells and elevated helper:suppressor (T4:T8) ratios. In additional experiments using isolated populations of T-cell subsets, T8 cells from MS patients who had low percentages of circulating T8 cells were found to suppress PWM-induced IgG secretion by autologous cells to a similar extent as controls, suggesting that in vitro, T8 cells function normally in these patients. In vitro IgG secretion by unstimulated mononuclear cells in MS appears to be a further reflection of abnormal immune regulation in this disease.