An orally active inhibitor of the angiotensin-converting enzyme, SQ 14,225 (D-2-methyl-3-mercaptopropanoly-L-proline), was administered to fourteen normal male volunteers to evaluate its safety and efficacy in inhibiting pressor responses to exogenous angiotensin I. SQ 14,225 produced significant blockade within 15 min of oral administration. The magnitude and duration of inhibition were dose-related. After a dose of 20 mg, complete blockade was observed for more than 2 h and partial inhibition for over 4 h. There was no effect on pressor responses to angiotensin II. SQ 14,225 promises to provide a new approach to the diagnosis and treatment of disorders involving over-activity of the renin-angiotensin system.