The present investigation was carried out to study the effect of aging on the activation of murine peritoneal macrophages by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) to tumoricidal state. Age-dependent alteration in macrophage-mediated tumor cell binding, cytotoxicity, cytostasis and production of the tumoricidal effector molecules oncostatin M, tumor necrosis factor and nitric oxide (NO) was studied. Macrophages (1.5 x 10(5)) obtained from mice of different age groups were separated on the basis of the reproductive status of the mice into prereproductive (young), reproductive (adult) and postreproductive (old) for studying their activation. Macrophages obtained from the old mice were found to be least responsive to the activation signal of LPS + IFN-gamma for macrophage-mediated tumoricidal activity and production of effector molecules. The macrophages of the old mice did not express inducible nitric oxide synthase, an enzyme responsible for the production of NO by activated macrophages. Macrophages of the adult and young groups showed better response; however, optimal response was observed in the macrophages of adult mice. The reasons for the observed difference in the response of macrophages are discussed.