The effects of antenatal phenobarbital on behavioral state and heart rate (HR) were examined in a randomized sample of 49 preterm infants > 24 and < 34 weeks postconceptional age. Behavioral state and HR observations were made during a routine care giving procedure on Days 1, 2, and 3 of life. There were no differences in behavioral state and HR responses between control and experimental subjects, suggesting that antenatal phenobarbital did not have a sedative effect on experimental subjects. Infants in both study groups responded to caregiving with changes to fussy/cry behavior and increases in HR. Older infants and nonventilated infants were more often in fussy/cry states during care giving than younger infants and ventilated infants. The HR increases were not clinically important, but the behavioral changes were, suggesting that behavioral response may be a more sensitive sign of distress than HR in very young preterm infants.