Extracts prepared from spontaneous mouse mammary adenocarcinomas, as well as plasma and urine from inbred C3H/HeN mice carrying murine mammary tumor virus and bearing such tumors, significantly inhibited the accumulation of macrophages at inflammatory sites in inbred the accumulation of macrophages at inflammatory sites in inbred C3Heb/FeJ mice. Much of the inhibitory activity from tumor cells was associated with products having a molecular weight (¿ 30,000); the inhibitory factor isolated from the plasma and urine of tumor-bearing animals had a molecular weight of 30,000 or less. Liver and spleen tissue, plasma, and urine from non-tumor-bearing animals had a molecular weight of 30,000 or less. Liver and spleen tissue, plasma, and urine from non-tumor-bearing animals had no effect on macrophage accumulation. Tumor cell extracts, plasma, and urine from tumor-bearing mice were shown to be free of infectious lactate dehydrogenase virus, a frequent contaminant of transplanted tumor and a known modifier of macrophage function. These results agreed with earlier reports of inhibitory activity for macrophage accumulation found in the tumors and sera of mice bearing multiple-passaged transplanted tumors and suggested that spontaneously arising neoplasms may subvert immune surveillance by depressing the ability of macrophages to respond to inflammatory stimuli.