The effect of biomaterials on the superoxide-producing ability of neutrophils was studied. Human peripheral blood neutrophils were incubated with cobalt-base alloy (F-75) or polystyrene beads of a nonphagocytosable size. Respiratory burst activity was studied by measuring superoxide dismutase inhibitable reduction of cytochrome C. Neutrophils were found to release no more superoxide anion on incubation for up to 3 h with either material in a protein-free medium than controls without foreign material. However, the ability of neutrophils incubated with either biomaterial to subsequently respond to phorbol myristate acetate challenge was decreased (p less than 0.05). Chemical analysis of supernatants for the F-75 samples showed a high concentration of cobalt in the medium within 1 h of incubation. Minimal chromium and nickel was detected. No correlation could be demonstrated between metal in solution and the respiratory burst defect in neutrophils. Instead it appears that interaction of cells with either surface was the critical event in altering the response to phorbol myristate acetate. This observed functional defect may play an important role in rendering tissue around implanted biomaterials susceptible to infections.