Proteolipid protein (PLP) is the major protein of central nervous system (CNS) myelin. In some species, intradermal inoculation with PLP and adjuvants causes experimental autoimmune encephalomyelitis (PLP-EAE) characterized by neurological signs of tail and limb weakness and by inflammation and demyelination in the CNS. A previous study found that inoculation of Lewis rats with 100 micrograms of PLP causes PLP-EAE with a low incidence of neurological signs and a highly variable clinical course. In the present study we assessed PLP-EAE produced by inoculation with 1000 micrograms of PLP per rat. Fifty-one of 59 (86%) Lewis rats developed neurological signs 8 to 20 days (mean = 12.0 +/- 2.0) after inoculation with 1000 micrograms of PLP. In such rats, mononuclear cell infiltrates were present in the brain and spinal cord while primary demyelination occurred mainly in the subpial regions of the spinal cord, especially in the dorsal root entry and ventral root exit zones. The histological findings were compared with those in acute EAE induced in the Lewis rat by inoculation with whole CNS tissue or with myelin basic protein: in PLP-EAE, in contrast to these other models, the disease was essentially restricted to the CNS. This form of EAE should be useful in future studies of the consequences of autoimmunity to PLP.