The purpose of this study was to determine the effect of chronic blockade of the brain renin-angiotensin system on the hormonal response to stress in spontaneously hypertensive rats (SHR). To this end, we measured changes hi plasma corticosterone, vasopressin, plasma renin activity, aldosterone, norepinephrine, and eplnephrine in SHR treated with a 4-week intracerebroventricular infusion of captopril (osmotic minipump, 1.25 μg/hr) or vehicle in response to cold stress (4 °C × 4 hours) or ether stress (5 minutes). Within the fourth week of treatment, the average systolic blood pressure of captopril-treated SHR was significantly lower than that of vehicle-treated rats. Basal plasma levels of corticosterone, but not vasopressin, were significantly lower in SHR treated with captopril. In response to cold stress, captopril-treated SHR showed significantly lesser increases in both corticosterone and vasopressin than did vehicle-treated SHR. There were no differences in basal plasma levels of norepinephrine, epinephrine, plasma renin activity, or aldosterone between captopril-treated and vehicle-treated SHR, and both groups showed elevations of a similar magnitude after exposure to cold. In response to ether stress, captopril-treated SHR also showed significantly smaller increases in corticosterone and vasopressin than did vehicle-treated SHR. These results suggest that chronic intracerebroventricular administration of captopril, through blockade of the brain renin-angiotensin system, alters the hormonal response of SHR to stress. © 1988 American Heart Association, Inc.