Macrophage-rich peritoneal cell populations from C57BL/6 mice grafted with DBA/2 skin were found to be cytotoxic against 51Cr-labeled target cells from the donor strain. Normal peritoneal macrophages were also rendered cytotoxic by incubation with acellular supernatants of mixed lymphocyte cultures (MLC) between an allograft recipient and a donor mouse. Supernatants alone were not cytotoxic. The macrophage arming factor(s) was found in supernatants when the MLC was performed after more than 6 to 9 days following grafting. In order to produce MAF, sensitized lymphocytes must usually be stimulated in a specific way by donor type cells. The armed macrophage cytotoxicity was, however, not found to be specific in these experiments.