Complement-dependent gliotoxic antibody activity was determined in 22 patients with multiple sclerosis (MS) and 19 normal control persons. Peripheral blood serum was collected from MS patients at about 4-week intervals for one year, and the results of cytotoxicity tests correlated with the course of disease. For 10 MS patients with stable disease, complement-dependent cytotoxic antibodies directed against a noncytocidally infected mouse glial cell line (an as yet unidentified virus) were found in significantly higher than normal titer. For 12 MS patients with fluctuating clinical course, the gliotoxic antibody titer remained relatively constant before relapse. During relapse, the titer remained constant or dropped. With remission initially low titers increased appreciably.