Generation of oxygen metabolites is an important component of the neutrophil's armamentarium against microbes. Production of superoxide anion (O−2) and generation of hydroxyl radical (OH) were measured in neutrophils from cord blood of 12 vaginally delivered, term newborn infants and 12 adults after stimulation with phorbol myristate acetate (PMA) and opsonized zymosan. With either stimulus, generation of OH was relatively less than production of O−2for all infants studied. This discrepancy might be related to abnormal release or diminished cell content of a cofactor necessary for production of OH from O−2Since both lactoferrin (LF) found in specific granules and myeloperoxidase (MPO) found in azurophilic granules have been shown to enhance OH generation, we compared degranulation of both granule types in response to PMA and opsonized zymosan and total neutrophil content of MPO, LF, and lysozyme in cord blood and adult neutrophils. Degranulation, even after pretreatment with cytochalasin B, was the same for newborn and adult neutrophils. Content of MPO was identical (adult, 204 ± 24Aunits, mean ± SEM,n= 9; newborn, 201 ± 21,n= 9) but lysozyme was mildly diminished (adults, 111 ± 10Aunits; newborn, 89 ± 6,n= 9,p< 0.05), and lactoferrin was moderately decreased (adult, 89.0±7.3 μg/mg cell protein,n= 11; newborn, 43.2±7.0,n=11 < 0.005). Generation of Oh in response to PMA and LF content were measured in seven cord blood-adult control pairs. Both LF and OH generation were diminished in newborn cells and there was a direct relationship between OH generation and LF content. Electron microsopic studies of newborn neutrophils demonstrated evidence of degranulation and loss of specific granules. these dificits may be related to defective bactericidal activity exhibite by neutrophils from neonates. Activation of neutrophils during partuition may be the cause of the decrease in specific granules and the diminished LF content.