A consecutive cohort of 87 infants (46 infants less than 37 weeks gestational age and 41 term infants greater than or equal to 37 weeks gestation) admitted to the Neonatal Intensive Care Unit (NICU) and a convenience cohort of 27 term well babies at the University of Nebraska Medical Center (Omaha, NE) were evaluated for plasma beta-endorphin (beta E) levels during the first 4 h after birth. Demographic data, maternal history, and respiratory status at the time of sampling as well as development of documented apneic episodes during the initial hospitalization were analyzed for all infants. All NICU infants had higher plasma beta E levels than the control infants. Premature infants had significantly higher neonatal plasma beta E levels than term infants in either the control or NICU groups, but the response was gender specific; premature males had higher plasma beta E than premature females (P = 0.008). Perinatal stress, including respiratory problems, was associated with the increase in plasma beta E, but prematurity and being male were significantly predictors of an elevated plasma beta E level. Immaturity in respiratory control, as evaluated by the development of documented apneic episodes during the infant's initial hospitalization, did not correlate with an elevated perinatal plasma beta E level.