Experimental allergic encephalomyelitis (EAE) was elicited in donor Lewis rats by immunization with heterologous spinal cord antigen and adjuvants. Suspensions of cells from their draining lymph nodes transferred the disease passively to normal isohistogenic Lewis recipients and to genetically tolerant (Lewis X BN) or (Lewis X Buffalo)F1 hybrids, in all of which Lewis cells should enjoy extended survival. However, in accordance with the rules of transplantation genetics responsible for homograft rejection, transfers of such Lewis cells to normal BN, Buffalo, ACI and Wistar/Furth recipients were not effective, nor were transfers of cells from immunized hybrid donors to normal Lewis recipients. Donor cells would not be expected to survive in these situations. On the other hand, transfers of immmunized Lewis cells to Fischer 344 recipients were successful, especially after adrenalectomy of recipients or focal impairment of their blood-brain barrier by cyanide treatment. This inter-strain transfer of EAE was attributed to genetic identity of these two strains at a major histocompatibility locus, and was obtained despite differences at minor histocompatibility loci. There was no evidence of a significant Y-linked histocompatibility factor in this system.