Two pentapeptide analogues of the ketomethylene-containing angiotensin converting enzyme (ACE) inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and evaluated as ACE inhibitors and antihypertensive agents. Compounds 14 and 15 were very potent ACE inhibitors with I50 values of 7.0 and 3.0 nM, respectively, compared to an I50 value of 70 nM for 1. Neither 14 nor 15 showed significant blood pressure lowering activity in renal hypertensive rats. Investigations conducted on a tritiated analogue of 14 showed that 70% of an oral dose of this compound is absorbed but is rapidly excreted from the blood with a half life of 24 min. Thin-layer chromatography of bile and urine contents in rats given tritiated 14 orally showed that it is excreted in greater than 90% unchanged form. This implies that a ketomethylene linkage can stabilize peptide amide linkages adjacent to it to peptidase degradation.