In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with $IFN-gamma$. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-, had a very low activating effect. Following preincubation with both protein A and $IFN-gamma$, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-$alpha$ or the inhibition of NO Production, TNF-$alpha$ and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with $IFN-gamma$. We also demonstrated that supernatants from macrophages treated with protein A plus $IFN-gamma$ contained both TNF-$alpha$ and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-$alpha$ or NO. These results demonstrate the synergistic effects on mouse pertioneal macrophage function of protein A in combination with $IFN-gamma$ and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.