When guinea-pig polymorphonuclear leukocytes (PMNs) are stimulated with hen ovalbumin (OA)-complexed IgG antibodies, they generate superoxide anion (O2-). This reaction was found to depend on the IgG isotype used for preparation of the immune complexes; OA-complexed IgG2 antibody (OA-IgG2) induced 3-4 times more intensively O2- generation than OA-complexed IgG1 antibody (OA-IgG1). The O2- generation with OA-IgG1 was almost completely inhibited by a monoclonal antibody to the Fc gamma R binding both IgG1 and IgG2 (Fc gamma 1/gamma 2 R), whereas that with OA-IgG2 was only slightly inhibited. Since guinea-pig PMNs are capable of binding OA-IgG2 not only through Fc gamma 1/gamma 2 R but also through another Fc gamma R which is specific for IgG2 alone (Fc gamma 2 R), the O2- generation with OA-IgG2 may be mainly mediated by Fc gamma 2 R. In addition, cytochalasin B was found to enhance markedly the O2- generation with OA-IgG1, though that with OA-IgG2 was only slightly affected. The results so far obtained indicate that Fc gamma 1/gamma 2 R and Fc gamma 2 R differ from each other in their activities for triggering O2- generation, namely activation of the respiratory burst NADPH oxidase. Furthermore, differing from the activation of the NADPH oxidase mediated by Fc gamma 2 R, that by Fc gamma 1/gamma 2 R was shown to be suppressed by some cytochalasin B-inhibitable factor or process though its biochemical nature is unknown.