Even though IgA is considered to play an important role in immunity, surprisingly little is known about the presence of IgA Fc receptor (Fc alpha R)-expressing effector cells in tissues. Difficulties in obtaining human tissue macrophages, led us to study peritoneal macrophages in a human Fc alpha RI transgenic (Tg) mouse model. Naive peritoneal macrophages did not express hFc alpha RI. Expression, however, could be induced by overnight culture, and was upregulated by GM-CSF. In addition, the receptor proved functional since macrophage-mediated phagocytosis and tumor cell kill were effectively triggered via hFc alpha RI. To assess necessity of the FcR gamma-chain signaling molecule for hFc alpha RI function in macrophages, Tg mice were crossed with mice deficient in FcR gamma-chain (gamma-/-). Tg, gamma-/- macrophages were unable to kill tumor cells. This, because Tg macrophages failed to express hFc alpha RI in the absence of FcR gamma-chain, and overnight culture did not overcome this lack of expression. Further studies with the transgenic mouse model presented in this study will help to define the precise conditions under which Fc alpha RI is expressed on macrophages. It will, furthermore, represent a useful tool to study Fc alpha RI function in immune defense.