Experimental allergic encephalomyelitis (EAE) was induced in inbred Lewis rats by sensitization with bovine white matter proteolipid apoprotein (PLP). 18-61 days after a single injection of 100 micrograms of PLP, 12 of 31 rats (39%) developed clinical EAE and 18 of 23 (78%) showed pathologic EAE with significant demyelination. Lymphocyte proliferative responses and antibodies to PLP were elevated but did not correlate with the clinical or pathologic state. This is the first demonstration of PLP-induced EAE with significant demyelination in rats and will contribute to the study of autoimmune demyelination.