The effects of exogenous corticotropin releasing factor and arginine vasopressin were evaluated in 6-and 11-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Basal adrenocorticotropic hormone (ACTH) and vasopressin levels did not differ between SHR and WKY, but basal corticosterone level was higher in 6-week-old SHR (p< 0.01). To block endogenous corticotropin releasing factor secretion and nonspecific systemic responses, both groups were pretreated with chlorpromazine, morphine, and sodium pentobarbital anesthesia before measurement of ACTH responses to corticotropin releasing factor and vasopressin infusion. Basal ACTH level was lower in anesthetized 6-week-old SHR than in age-matched WKY (p< 0.01), but no difference was seen between 11-week-old WKY and SHR. The ACTH response to corticotropin releasing factor in 6-week-old WKY was significantly greater than that in age-matched SHR (p< 0.01), whereas in 11-week-old SHR and WKY the response was similar. Compared with responses in WKY, SHR showed an increased ACTH response to high doses of vasopressin (0.25 μg/100 g body weight) at both ages (p< 0.05). These results indicate that the ACTH response to corticotropin releasing factor is blunted in the early stages of hypertension in SHR but later recovers. These abnormal responses to corticotropin releasing factor and vasopressin may be related to the development of spontaneous hypertension.