Enflurane and isoflurane, widely used general anesthetic agents, were shown to significantly inhibit the microbicidal oxidative activity of pulmonary alveolar macrophages (PAM) at clinically relevant concentrations. This inhibition was reversible, as exposing the anesthetic-treated PAM to air for 30 min completely removed any depression of oxidative activity. Using chemoluminigenic probes to analyze the generation of oxidative metabolites, a significant reduction in superoxide anion (O2-) production was found in PAM exposed to enflurane or isoflurane.