Mice were infected with Friend leukemia virus and later immunized with either Vibrio cholerae vaccine or sheep erythrocytes. The primary antibody response to the bacteria (as judged by the number of plaque-forming cells) was slightly enhanced by the viral infection, whereas the response to sheep erythrocytes was inhibited. The difference appeared due to sensitization of mice to antigens crossreacting with those of sheep erythrocytes; no natural immunity to V. cholerae is detectable. However, the response of mice infected with Friend leukemia virus to a secondary challenge with the cholera bacteria was markedly inhibited. Even though the number of plaque-forming cells during the primary response was not reduced, accumulation of the cells in distinct splenic foci was suppressed. These results suggest that the effect of Friend leukemia virus on immunocompetent cells is selective. The immune response appears to be susceptible to leukemia virus-induced immunosuppression only when there has been a previous stimulation of immunocytes by antigen.