Guinea-pig macrophages respond to ovalbumin (OA) complexes of IgG antibodies with the extracellular release of arachidonic acid (AA). The AA release by OA complex of IgG2 antibody (OA gamma 2) was found to occur more intensively than did that by OA complex of IgG2 antibody (OA gamma 1). To clarify the roles of the Fc gamma receptor (Fc gamma R) for IgG2 alone (Fc gamma 2R) and that for both IgG1 and IgG2 (Fc gamma 1/gamma 2R) in these responses, the effects of Fab's of monoclonal anti-Fc gamma 2R and anti-Fc gamma 1/gamma 2R antibodies were examined. Anti-Fc gamma 1/gamma 2R Fab' inhibited completely the response to OA gamma 1. The response to OA gamma 2, on the other hand, was not inhibited by anti-Fc gamma 1/gamma 2R Fab', but by anti-Fc gamma 2R Fab'. By cross-linking of the Fc gamma Rs, the ability of Fc gamma 2R to trigger the AA release was found to be 2-3 times greater than its Fc gamma 1/gamma 2R counterpart. The Fc gamma 1/gamma 2R-mediated response to OA gamma 1 was completely inhibited with EGTA. In contrast, the Fc gamma 2R-mediated response to OA gamma 2 was not affected at all with EGTA, though it disappeared on depletion of the intracellular Ca2+ of macrophages with EGTA and Ionomycin. In conclusion, the mechanisms of Fc gamma 1/gamma 2R- and Fc gamma 2R-mediated signal transduction leading to the AA release differ from each other in the dependency upon the Ca influx.