CS-622 is a prodrug type ACE inhibitor with a thiazepin ring. Its active form, CS-622 diacid, was slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of CS-622 diacid on isolated rat aorta was 3 times that of enalaprilat. The inhibitory action of enalaprilat was abolished quickly by washing the aortic strip with drug-free solution, whereas that of CS-622 diacid was abolished only slowly. This difference suggests that CS-622 diacid binds to vascular ACE more firmly than enalaprilat. By oral administration, CS-622 was 3 times more potent than enalapril, and its onset of action was faster than that of enalapril, suggesting that the conversion of CS-622 to its active diacid occurs faster than the conversion of enalapril. Although CS-622 diacid was only slightly more potent than enalaprilat by intravenous administration, it had a longer duration than enalaprilat. Elimination of renal excretory function potentiated the action of captopril but not that of CS-622, suggesting that unlike captopril, only a small portion of CS-622 is excreted through the kidney.