The capacity of humoral antibody to confer protection against Venezuelan equine encephalomyelitis (VEE) infection did not require participation of cellular components of the immune response. Likewise, immune spleen cells conferred protection without participation of either preformed antibody or induction of an anamnestic antibody response. Time after donor immunization was a critical factor in determining the antiviral potential of transferred cells, and mice boosted with a second immunization of attenuated VEE virus did not have their antiviral capacity restored. Protection induced by transfer of immune spleen cells was immunospecific but could be inhibited by in vitro treatment of cell preparations with antithymocyte serum or anti-ϑ serum but not by treatment with anti-mouse γ-globulin. There was no evidence that preformed interferon contributed to the protective activity of passively transferred immune cells. Apparently, both humoral antibody and cellular immunity play important roles in protection against VEE virus infection in mice.