Oxidative metabolic responses of polymorphonuclear leukocytes were assessed in 24 stressed neonates and 22 well, term infants utilizing particulate and soluble stimuli. Stressed neonatal PMNs demonstrated a depressed CL response to zymosan, whereas O2- production for both normal and stressed PMNs of neonates was significantly elevated compared to that in PMNs from adults. These results were not ascribable to phagocytosis since it was comparable in all groups using radiolabeled bacteria. Stressed neonates' PMN responses to soluble stimuli were significantly elevated when compared with those from well neonate and adult controls. Enhanced responses were most prominent in the most severely stressed infants. Treatment of neonates' PMNs with the antioxidants vitamin E and DHB partially corrected the abnormalities, suggesting peroxidative damage to the PMN membrane had occurred. The oxidative metabolic abnormalities of neonates' PMNs are consistent with either a defect in HMPS activity, a defect in functioning of the later portions of the respiratory burst, or a stimulus-specific abnormality in respiratory burst activity.