The superoxide (O2-) generating activity of human polymorphonuclear leukocytes (PMN) was suppressed more than 50% compared with control cells by preincubation of the cells with soluble immune complexes (Fc receptor-mediated desensitization). The suppression was observed when wheat germ agglutinin (WGA) or N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) was used as stimuli for O2- generation. However, the desensitized cells could produce as much O2- as control cells when they were stimulated with phorbol myristate acetate (PMA). The desensitized cells were pre-exposed to a small dose of PMA for a short period (2-3 min). By this procedure, the activity of the cells for WGA or fMLP induced O2- generation was almost completely restored. Similarly, the inhibitory effect of 3'-deazaadenosing on WGA, fMLP or immune complexes (IC) induced O2- generation was abolished by the short-term pre-exposure of the cells to a small dose of PMA.