Summary When adult rats were immunized with sheep erythrocytes, the secondary hemolysin response was lower than the primary response. The effect of circulating hemolysin on the rat's response to sheep erythrocytes was investigated. A marked inhibition of the primary hemolysin response in the rat was produced by administering homologous anti-sheep erythrocyte serum 24 hr before the injection of sheep erythrocytes. Significant inhibition of the antibody response occurred with a wide range of doses of antiserum and antigen. Inhibition of the antibody response by antiserum occurred when rats were actively immunized intravenously, intraperitoneally, or intradermally. The presence of circulating hemolysin was necessary to demonstrate the inhibition of the hemolysin response. Unresponsiveness to antigenic stimulation induced by a single passive immunization was sustained if small doses of sheep erythrocytes were injected at weekly intervals. The possible mechanisms responsible for this phenomenon were discussed.