We have been studying genetic differences in susceptibility to autoimmune encephalomyelitis (EAE) between Strain 13 (susceptible) and Strain 2 (resistant) guinea pigs. Strain 2 sensitized to guinea pig spinal cord antigen shows histological evidence of, but not clinical signs of EAE. In reciprocal crosses to produce F1 offspring, the females (if not the males) should normally be identical in degree of resistance to EAE. Surprisingly, the 2 x 13 females are more determining the outcome. The nature of this effect, and the differences between subpopulations of guinea pig T cells are being examined by cellular immunological approaches. The heterogeneity of T cell functions in being approached in mouse systems because of availability of suitable animals, and the current knowledge of their lymphokines.