During the last 2 days of pregnancy in rats, basal corticosterone secretion is enhanced, although the response of the hypothalamo-pituitary-adrenocortical (HPA) axis to emotional and physical stressors is blunted, independent of the action of endogenous opioids. In this study, alterations in the reactivity of the HPA axis, which may accompany parturition-related stimuli, and the involvement of endogenous opioids were examined in chronically catheterized rats. In vehicle-treated controls (n = 9), ACTH and corticosterone secretion decreased in preparation for birth (P < 0.01) and further declined immediately after delivery of the second pup (P < 0.01), remaining low for 150 min. In contrast, in animals injected with the opiate antagonist naloxone (5 mg ml(-1) kg(-1), i.v., n = 6) after delivery of the second pup, ACTH and corticosterone release were enhanced within 20 min (ACTH, 5.0-fold; corticosterone, 2.3-fold; P < 0.01 vs. controls) and returned to control levels after 90 min. In confirmation of previous reports, oxytocin secretion into blood was elevated in control rats after the onset of parturition (P < 0.01) and was further enhanced in the naloxone group (1.4-fold, P < 0.01 vs. control). Plasma lactate concentration was increased, 30 min after the onset of delivery (1.9-fold, P < 0.01), independent of the treatment. The data indicate that parturition-related events do not trigger HPA axis hormone release because of an effective inhibition by endogenous opioids. This nonresponsiveness of the HPA axis is likely to protect the pups' well-being during birth.