Sera from normal mice and mice bearing murine mammary tumor virus (MTV)-induced tumors showed cytotoxic reactions to the MTV-producing Mm5mt/c1 cell line. The reaction could be blocked by the addition of MTV, but not of purified gp52 and p28. In sera from tumor bearers, cytotoxic responses ranged from 15 to 66%; reactivity was generally highest when the serum was diluted 32 to 128 times. The cytotoxic sera from the normal animals showed a much lower activity; again, there was a lack of cytotoxic response at lower serum dilutions. Low dilutions (1 to 64) of sera from tumor-bearing and normal mice were found to inhibit the MTV-specific cytotoxic activity of rabbit anti-MTV serum on the Mm5mt/c1 cell line. Specificity of this phenomenon was deduced from the fact that there was less inhibition by the mouse sera of anti-Rauscher leukemia virus-specific cytotoxic activity to Rauscher leukemia virus-infected cells and of anti-vaccinia virus serum to vaccinia virus-infected cells. Absorption of the mouse sera with rabbit anti-gp52 serum almost completely abolished the inhibition; after absorption with MTV, inhibition was somewhat reduced. The effect of free gp52 and MTV/anti-MTV immune complexes on the anti-MTV immune response is discussed.