The total and mite antigen-specific IgE in the sera were measured in 60 patients with multiple sclerosis (MS) and 40 healthy controls by an enzyme-linked immunosorbent assay using two common mite antigens, Dermatophagoides farinae and Dermatophagoides pteronyssinus, in order to study the role of atopy in MS. Neither the total IgE level nor the frequency of mite antigen-specific IgE differed significantly between the MS patients (mean total IgE 162 U/ml, 42% mite IgE-positive) and healthy controls (mean total IgE 168 U/ml, 35% mite IgE-positive). The MS patients with mite antigen-specific IgE showed a significantly higher level of serum total IgE (mean 293 U/ml, P=0.0005) and a higher frequency of atopic disorders (36%, P=0.0508) than did the MS patients without mite antigen-specific IgE (mean total IgE 68 U/ml, atopic disorders 14%). The former group also showed a significantly higher frequency of male (P=0.0216), a younger age of onset (P=0.0081), a lower expanded disability status scale (EDSS) score (P=0.03) and a lower protein content in the cerebrospinal fluid (CSF) (P=0.0426) than the latter, while the duration of disease and a number of relapses did not differ significantly between the two groups. In addition, the mite IgE-positive MS showed a very low frequency of oligoclonal IgG bands in CSF (4%) and a significantly higher association of HLA-A24 (87.5%) than the healthy controls (45%). Therefore, the presence of IgE response to the mite antigens and atopy appeared to significantly lessen the severity of the disease and the immunologic abnormalities in MS.