Two hundred fifty-four MS patients were studied for circulating immune complexes (CIC) by three different assays: Raji-RIA, Clq-PEG, and Conglutinin-BA. Thirty-five percent of the sera were positive by one or more of these tests; Raji-RIA had the highest sensitivity (29.4%). Incidence of CIC in acute relapse, progressive, remission, and stable state of MS was 33.3%, 30.2%, 26.1%, and 23.1%, respectively, by Raji-RIA, compared with 7.75% and 8.82% among normal and neurologic controls. The incidence of CIC in neurologic controls differed significantly from both acute relapse and progressive disease, and almost significantly from patients in remission. There was no significant difference between patients with stable MS and neurologic controls, and there was no association of CIC with HLA-B7.