Acute lung injury induced by meconium aspiration is characterized by rapidly developing pulmonary inflammation with influx of activated polymorphonuclear cells. To evaluate the role of meconium in the activation of these invading cells, we described the oxidative capacity of circulating neutrophils after intratracheal administration of thick human meconium in pigs. We also examined the direct effects of varying meconium concentrations on the oxidative burst of human neutrophils in vitro. In neutrophils isolated from meconium-insufflated pigs, phorbol myristate acetate stimulation led to an average 11.7-fold increase in production of reactive oxygen species, measured by chemiluminescence, whereas the increase in control cells from saline-instilled pigs was only 3.1-fold, p =.012 between the groups. Activation of unstimulated human leukocytes by meconium resulted in a dose-dependent response. The lowest meconium concentration (0.2 mg/mL) had an inhibitory effect on neutrophil activation, whereas higher concentrations of meconium (1 and 2 mg/mL) increased neutrophil oxygen radical production progressively. These results thus indicate that moderate and high concentrations of aspirated meconium rapidly activate circulating neutrophils with a resulting oxidative burst contributing to pulmonary tissue injury, whereas low contamination of the aspirated material may in fact suppress the development of oxidative lung injury.