Captopril, an orally active inhibitor of angiotensin-I-converting enzyme, was administered in a single dose to five anephric patients who had extremely low plasma renin activities. The drug did not lower blood pressure or significantly alter plasma renin activity in any patient but increased mean arterial pressure slightly in three. These results suggest that the blood-pressure lowering effect of captopril depends on an active renal renin-angiotensin system. Though additional mechanisms, such as accumulation of vasodilator kinins resulting from kininase II inhibition, may also contribute to captopril's action, these mechanisms apparently require the presence of the kidney to have a clinically detectable effect.