Alacepril (1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine, DU-1219) showed a dose related and long lasting antihypertensive effect in renal hypertensive rats (two-kidney, one-clip), a typical renin dependent hypertensive model. The maximum hypotensive potency of alacepril (1-30 mg/kg) after single oral administration was slightly weaker than that of captopril (1-30 mg/kg). Judging from the AOC (area over the antihypertensive curve) value, the overall antihypertensive activity of alacepril was 3 times more potent than that of captopril on a weight basis. The long lasting antihypertensive effect of alacepril in renal hypertensive rats was also confirmed by once daily successive oral administration (1-2 mg/kg/d). In renal hypertensive dogs, alacepril (3 mg/kg) showed a stable and sustained hypotensive effect, and its duration of action was longer than that of captopril. Although alacepril did not possess a significant in vitro angiotensin converting enzyme (ACE) inhibitory activity, orally given alacepril (5.6-56.1 mg/kg) produced a potent and prolonged in vivo ACE inhibition which was estimated by suppression on angiotensin-I (310 ng/kg i.v.) induced pressor response in conscious normotensive rats. The prolonged in vivo ACE inhibitory activity of alacepril (5.6 mg/kg) was also observed in conscious normotensive dogs. These results suggest that the disposition and metabolism of orally given alacepril are responsible for the prolonged ACE inhibition and, concomitantly, for exerting the long lasting antihypertensive effect. Consequently, alacepril is a novel orally active ACE inhibitor having a potent and prolonged antihypertensive activity, and these properties suggest that alacepril is favorable for the treatment of hypertension.