Human myelin basic protein (hMBP) and proteolipid protein (PLP) were used as antigens in a solid-phase radioimmunoassay to determine relative frequencies of anti-MBP and anti-PLP in cerebrospinal fluid (CSF) of optic neuritis and multiple sclerosis (MS) patients. Forty-nine of 55 patients with optic neuritis had increased CSF anti-MBP and the remaining 6 had increased anti-PLP. Of 385 MS patients, MS relapse: 173 of 180 patients had increased anti-MBP, 5 of the remaining 7 patients had elevated anti-PLP, and 2 had neither of these autoantibodies. Progressive MS: 111 of 116 patients had increased anti-MBP in either free and/or bound form, of the remaining 5 patients 4 had increased anti-PLP, and 1 had neither anti-MBP nor anti-PLP. MS remission: 15 of 87 patients had somewhat increased anti-MBP, none had anti-PLP. IgG was purified by affinity chromatography from necropsy central nervous system (CNS) tissue samples of 4 individual patients with clinically definite and neuropathologically confirmed MS. Three of these 4 patients who had increased levels of CSF anti-MBP also had increased anti-MBP titers in CNS tissue-extracted IgG. The fourth patient who had anti-PLP in CSF also had anti-PLP in brain tissue IgG. These autoantibodies were not detected simultaneously in any patient. These results suggest that there are at least two immunologically distinct forms of MS, i.e., a common form highly associated with anti-MBP and more frequent prominent inflammatory characteristics in CSF and CNS, and an infrequent form associated with anti-PLP in CSF and tissue, and less abundant inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)