Although infection is a serious complication associated with the use of orthopedic prosthetic implants, the impact of the metal used in these devices on host defense is poorly understood. The authors investigated the effect of stainless steel, titanium, titanium alloy, and cobalt-chromium alloy on the respiratory burst of polymorphonuclear leukocytes (PMN), a vital component of bactericidal activity. In the presence of stainless steel powder or supernatants obtained from the incubation of stainless steel in buffer, superoxide production by PMN was significantly impaired. Titanium, titanium alloy, and cobalt-chrome alloy had no significant effect on superoxide production. Nickel and chromium, the only metal ions detectable in the stainless steel supernatant, did not impair superoxide production when tested at concentrations similar to those found in the supernatant. Inhibition of PMN superoxide production may play a role in the establishment and persistence of stainless steel device-related infections.