Exposure to zinc fume may cause metal fume fever, an acute reaction characterized by an invasion of neutrophils into the airways. This investigation was conducted to examine the possibility that Zn²⁺ and ZnO might stimulate the formation of oxygen radicals by human neutrophils. Luminol-amplified chemiluminescence (CL) was monitored during 2 h from human neutrophils exposed to Zn²⁺or ZnO. The response was compared to that of other metal ions and to that of endotoxin and phorbol myristate acetate (PMA). Zn²⁺ (6-50 mM) gradually caused a 2-6-fold increase of CL that reached an optimum after 70-80 min. By contrast, Cd²⁺, Cr²⁺, Cr³⁺, Fe²⁺, Fe³⁺, Ni²⁺ or Co²⁺ in corresponding concentrations did not increase the CL. Similar to Zn²⁺, endotoxin (40-640 mg/ml) caused a 2-5-fold increase of CL with an optimum after 70 min, and endotoxin (40 mg/ml) together with Zn²⁺ (50 mM) synergistically increased the CL. ZnO (12-100 mg/ml) also augmented CL, with a 1.5-5-fold increase at 25-100 mg/ ml ZnO but with a time response similar to that found after PMA stimulation, in which CL peaked after 20-40 min incubation. Both Zn²⁺- and ZnO-induced CL was inhibited by manoalide, a phospholipase A₂ inhibitor, with IC₅₀ of 0.25 mM and 0.66 mM respectively. These results indicate that Zn²⁺ and ZnO both stimulates oxygen radical formation in human neutrophils and that this might contribute to the pathogenesis of zinc fume fever.