AbstractCGS 13945 and CGS 13934 are two nonthiol ACE inhibitors having novel chemical structures. CGS 13945 is a monoester derivative of the free dicarboxylic acid CGS 13934. Based on studies from in vitro inhibition of ACE and in vivo inhibition of angiotensin I pressor responses, CGS 13945 must be hydrolyzed to CGS 13934 to express its optimal biological activity. Studies with rats reveal that CGS 13945 and CGS 13934 are orally effective inhibitors of ACE. Both inhibitors have a longer duration of action and are somewhat less effective than captopril. After oral administration, the bioavailability of the monoester CGS 13945 is greater than that of the free dicarboxylic acid CGS 13934. In the dog, CGS 13934 (i.v.) effectively inhibits angiotensin I pressor responses, but the esterified compound (CGS 13945) has only weak activity. This difference is presumably due to limited hydrolytic capacity of endogenous plasma esterase(s) in this species. However, both CGS 13945 and CGS 13934 potentiate the vasodepressor responses to bradykinin without affecting angiotensin II pressor responses.