The objective of this study was to determine the consequences for HPA axis functioning among healthy full‐term newborns of prenatal treatment with the synthetic glucocorticoid (GC), betamethasone, which is the routine treatment for threatened preterm delivery. Ninety full‐term infants were recruited into two study groups (30 betamethasone treated; 60 comparison group matched for GA at birth and sex). The cortisol and behavioral response to the painful stress of a heel‐stick blood draw was assessed 24 hr after birth. Full‐term infants exposed to prenatal betamethasone displayed a larger cortisol response to the heel‐stick procedure, despite no differences in baseline levels. Further, within the recommended window of betamethasone administration (24–34 gestational weeks), infants exposed to betamethasone earlier in gestation displayed the largest cortisol response to the heel‐stick. These data add to accumulating evidence that prenatal exposure to elevated GCs programs the development of the HPA axis. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 53:175–183, 2011