The distribution of HLA antigens A, B, C and DR was studied in 69 native Alsatian multiple sclerosis (MS) patients. Antigen DR2 was high in MS compared to healthy control subjects, as is known. Given antigens were more frequently, and, above all, more closely linked with certain clinical and organic parameters. Antigens A3, B7 and B40 were preferentially associated with progressive forms, and A32 with remitting forms. B7 may be predictive of the prognosis, as it was correlated with disease severity. B7 and DR2 were more frequent in MS patients presenting intrathecal immunoglobulin synthesis. Sex appeared to be a fundamental factor in the clinical expression of MS, interacting closely with the HLA system. These findings confirm the multi-factor etiology of MS. Several MS susceptibility genes may exist near the HLA complex, and their expression may modulate the clinical and organic signs of MS. Studies of this sort should be carried out on ethnically and geographically homogeneous populations.