The effect of prolonged intracerebroventricular (i.c.v.) infusion of N-acetyl-pepstatin in young and adult spontaneously hypertensive rats was studied. In young animals, pepstatin infusion resulted in a decrease in blood pressure and heart rate. Water intake and body weight were not affected. The depressor effect was accompanied by a slight increase in plasma renin activity and decreases in plasma vasopressin and plasma catecholamines. The blood pressure of adult rats with already established hypertension was not significantly affected. In addition, changes in plasma renin or catecholamines were not observed in these animals while vasopressin levels were slightly increased. The involvement of a possibly decreased sympathetic activity in the depressor effect of pepstatin is suggested. It is concluded that increased brain renin activity contributes to the development of hypertension of spontaneously hypertensive rats.