The beta-endorphin (BE) response to surgical stress in newborns and infants and its relation to pituitary-adrenal dynamics during stress is still unknown. Nine newborns 5 h to 5 days of age, and 5 infants 5 to 10 months old undergoing surgery were studied. All patients were anesthetized with N2O–O2 and halothane. Blood samples for BE and cortisol determinations were taken preoperatively and 30 min, 12 h, and 24 h after operation for radioimmunoassay. Both BE and cortisol levels in newborns were not significantly different from those in infants preoperatively (196±85.2 pg/ml vs. 138±47.8 pg/ml for BE and 23.7±17.5 μg/dl vs. 10.1±5.6 μg/dl for cortisol, P >0.05). At 30 min after operation, no significant increase in BE (220±106 pg/ml) and cortisol (36.1±21.2 μg/dl) was found in newborns, while significant increases (BE 493±281 pg/ml, cortisol 43.9±24.2 μg/dl) were found in infants compared to preoperative levels (both P <0.05). A significant difference between groups was seen in BE but not cortisol levels 30 min after operation. Both BE and cortisol declined to preoperative values within 24 h after surgery. Our study showed significant BE and cortisol responses to surgical stress in infants, but not in newborns. Factors such as age-related differential responses to the same anesthetic technique, duration of operation, and developmental differences in stress response are considered responsible for the differences.