To determine whether prenatal exposure to ethanol alters the response of the beta-endorphin (beta-EP) system to stress, the effect of two types of stressful stimuli, ether and cold, was examined in the offspring of rats which during pregnancy were: (a) fed with an ethanol-containing diet; (b) pair-fed with an isocaloric sucrose diet; and (c) fed ad libitum with standard lab chow (basic control group). The effect of stress on the content of beta-EP in the serum, pituitary gland and hypothalamus, as well as on the serum corticosterone and hypothalamic corticotropin-releasing factor (CRF) content was examined. Pups prenatally exposed to ethanol had significantly higher serum beta-EP levels on Day 1 and higher serum corticosterone levels on Days 1-3 when compared to their pair-fed or basic controls. On all days tested pituitary beta-EP content was lower in the offspring of the ethanol-treated rats than in the control groups. There was no difference in the total hypothalamic beta-EP content between the three treatment groups; however, during the first 10 days of life a higher concentration (ng/mg protein) of beta-EP was observed in the hypothalami of the ethanol and the pair-fed group when compared to the basic control pups. Hypothalamic CRF levels, though significantly lower in the pups exposed to ethanol in utero than in the control groups on Day 3, increased significantly in the ethanol group between Days 14 and 22, while no significant change was observed during this period in either of the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)