Supernatants of high density cultures of mouse peritoneal macrophages were inhibitory to homologous lymphoid cells in vitro by a number of parameters: proliferation and survival of lymphoma cells was impaired, the immune response of spleen cells to sheep red cells and to Concanavalin A (Con A) was decreased. Inhibition was due to factor(s) with mol. wt of approximately 110,000 as estimated by gel filtration. Activity was stable to heating at 56 degrees, and was resistant to trypsin but not to pronase.