Serotonin (5-hydroxytryptamine, 5-HT) significantly and dose-dependently suppressed the luminol-enhanced chemiluminescence (CL) signal generated by polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate (PMA), but did not modify either lucigenin-enhanced CL or the reduction of superoxide dismutase-inhibitable cytochrome c. Moreover, stimulation of PMNs previously incubated with 5-HT resulted in a threefold increase in 5-HT equivalents bound to the proteins of PMN. The addition of catalase or sodium azide substantially reduced this binding. The present results suggest that 5-HT metabolism is mediated by H2O2 and myeloperoxidase (MPO) released by activated PMNs. Hence 5-HT could lower the bactericidal function of these cells by competition with hypochlorite formation from halides and MPO/H2O2.