We studied the effect of total or partial splenectomy on experimental autoimmune encephalomyelitis (EAE) development in rats with different genetic background after immunization with guinea pig basic encephalitogenic protein in Freund’s complete adjuvant. The operations did not affect some strains with a high susceptibility to EAE but may have reduced the EAE development in the Fischer strain, which shows only a weak susceptibility. In some hybrids and backcrosses, but not in others, splenectomy resulted in a clear-cut reduction of neurological signs of EAE. This effect may be ascribed to the elimination of contrasuppressive cell populations.