Normal human neutrophils triggered by secretory IgA (sIgA) displayed low levels of cytotoxicity towards non-sensitized red blood cells. Catalase completely impaired this non-specific cytotoxicity (NSC), while superoxide dismutase (SOD) significantly enhanced it, suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Three heme-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole, did not decrease NSC, but significantly enhanced it, suggesting that the mechanism involved is not dependent upon myeloperoxidase (MPO). Heat-aggregated IgG (HA-IgG) synergize with sIgA in promoting NSC. It was also found that gamma interferon significantly enhanced neutrophil-mediated NSC induced by sIgA, its effect being more dramatic on NSC triggered by low concentrations of sIgA. The significance of these results is discussed.