Prenatal stress alters the endocrine as well as the behavioral responses of rodents. Because of the reductions in both estradiol-induced and ether-induced prolactin (Prl) release reported in prenatally-stressed (P-S) rats, we were interested in whether prenatal stress might also modify the prolactin response of male and female rats to a moderate stressor in adulthood, viz., restraint stress. Timed-mated Sprague-Dawley females were exposed to a daily regimen of heat and restraint stress from days 15-22 of gestation. Control animals remained undisturbed throughout pregnancy. In adulthood, half of the male and female P-S and Control offspring were stressed by placing them in a Plexiglas restraint tube for 60 min (restraint stressed; S; referred to as P-SS and CS, respectively). The remaining half of the P-S and Control animals were left undisturbed (these were nonrestrained; NR; referred to as P-SNR and CNR, respectively). Blood samples (decapitation) were then collected from all animals and plasma was assayed for Prl content. P-SNR and CNR males did not differ in baseline Prl levels, nor did P-SNR and CNR females. Following the restraint stress in adulthood, P-SS males as well as PSS females exhibited significantly less of an increase in Prl relative to CS males and CS females, respectively. In addition, baseline Prl levels differed between the sexes, with females--regardless of prenatal condition--having higher plasma Prl levels than males. These sex differences were no longer evident following restraint stress. These data, in combination with other work in P-S animals in the areas of Prl release and stress responses, demonstrate that prenatal stress renders the rat less hormonally (Prl) responsive to stress, with the effect being more pronounced in the female.