The antibody response to the structural proteins of rubella virus was studied in patients with multiple sclerosis (MS). Irrespective of the antibody titer to whole rubella virus, the relative proportion of the IgG response to the surface glycoprotein E1 was diminished, and that to the surface glycoprotein E2 was elevated in MS patients when compared to a matched control population of normal health individuals or a group of patients with systemic lupus erythematosus and other collagen vascular diseases. No difference was observed in the response to the core protein of rubella virus on comparing the MS and normal control groups. This divergence in the relative antibody response to the viral surface proteins suggests that the vigorous antibody response to rubella virus reported in MS is not simply an expression of a nonspecific polyvalent B-cell response.