A chronic experimental allergic encephalomyelitis (EAE) has been produced in rabbits sensitized with bovine white matter proteolipid apoprotein. Eleven of 12 animals developed clinical disease one to six months after immunization with a single dose of the apoprotein. The clinical course was characterized by posterior ataxia, flaccid paralysis progressing to spastic paralysis, and incontinence. Spontaneous relapses and remissions were observed in 3 rabbits. Histologically, acute and chronic encephalomyelitis accompanied by primary demyelination were observed. Serum antibody production, assayed by both an enzyme-linked immunosorbent assay and an electroblot procedure, did not correlate with either the clinical course or the histopathological findings. Delayed hypersensitivity to proteolipid apoprotein was observed in all rabbits prior to the onset of clinical signs. The data suggest that lymphocytes specifically sensitized to the proteolipid may be involved in the pathogenesis of the demyelination in chronic EAE.