Neutrophil-mediated tumor cell lysis is more efficiently triggered by FcalphaRI (CD89), than by FcgammaRI (CD64). This difference is most evident in immature neutrophils in which FcgammaRI-mediated tumor cell lysis is absent. In this study, we show that FcR gamma-chain-dependent functions (such as Ab-dependent cellular cytotoxicity and respiratory burst), as well as signaling (calcium mobilization and MAPK phosphorylation), were potently triggered via FcalphaRI, but not via FcgammaRI, in immature neutrophils. Internalization, an FcR gamma-chain-independent function, was, however, effectively initiated via both receptors. These data suggest an impaired functional association between FcgammaRI and the FcR gamma-chain, which prompted us to perform coimmunoprecipitation experiments. As a weaker association was observed between FcgammaRI and FcR gamma-chain, compared with FcalphaRI and FcR gamma-chain, our data support that differences between FcalphaRI- and FcgammaRI-mediated functions are attributable to dissimilarities in association with the FcR gamma-chain.