The blood serum of patients with multiple sclerosis (MS) was capable of recruiting autologous as well as normal mononuclear leucocytes in specific antibody-dependent cellular cytotoxicity (ADCC) of rat glial tumor CCL 107/C 6 cells. The gliotoxic ADCC activity of MS patients was significantly higher than that of normal persons and patients with other neurological diseases. MS serum alone or in combination with guinea pig complement was not cytotoxic for glial targets, and MS leucocytes alone displayed only nonspecific natural killer (NK) cell activity, which did not differ from that of normal persons. MS ADCC activity was tissuespecific for glial cells, being almost negligible for embryonic human lung fibroblasts and nonspecific for HeLa cells. Gliotoxic ADCC activity was higher in more severely disabled MS patients than in those who were less disabled. Patients with chronic progressive MS displayed the most significantly raised ADCC activity against glial cells, while patients in a stationary state had almost normal ADCC activity.