Patients with multiple sclerosis (MS) from the two Montreal MS clinics, were divided into two groups: one group of 61 patients (MS type I) who had no clinical history of susceptibility to recurrent respiratory tract infections and a second group of 58 patients (MS type II) who had persistent susceptibility to such infections since childhood. All patients were typed for the HLA tissue antigens. The HLA antigen frequencies of the total MS patient population, and of MS type I and MS type II patients were compared to those of a normal control population and each other. The HLA-DR2 and B7 antigen frequencies were significantly increased compared to the normal controls for all MS patients. MS type I patients had an increased frequency for HLA-Bw42 and DRw8 antigens; the frequency of HLA-A29 was lower than in the controls and MS type II patients. MS type II patients had a significantly increased frequency for DR3 and some HLA-DR3-associated phenotypes (A1 + DR3; B8 + DR3; A1 + B8 + DR3) as compared to controls and MS type I patients. These results are consistent with the existence of genes linked to the HLA antigens, such as immune response genes, which control the resistance or susceptibility of the patients to infection, and suggest that these HLA antigens could be associated with a difference in the evolution of MS, as observed in the MS type I and II patients [21].