A single intramuscular injection of MnCl2 in mice caused an increase in macrophage functional activity. Spleen cell antibody-dependent cellmediated cytotoxicity (ADCC) against both chicken erythrocytes and P815 tumor cell targets was enhanced 24 hours following a single injection of MnCl2. Enhanced ADCC activity following MnCl2 treatment was not associated with a change in spleen cellularities compared with saline injected mice. Resident peritoneal macrophages from mice injected intramuscularly with MnCl2 displayed enhanced phagocytic activity for chicken erythrocytes in the presence or absence of opsonizing antibody. Enhanced cytolytic activity against P815 mastocytoma target cells and enhanced cytostatic activity against MBL-2 lymphoma target cell was also observed for non-elicited resident peritoneal macrophages from mice injected intramuscularly with MnCl2. There were no differences in the cellularity or relative number of adherent cells obtained from the peritoneal cavity of saline or MnCl2 injected mice. These enhanced macrophage functions were associated with the induction of increased interferon levels in mice injected with MnCl2.