Different oral doses (5, 20, 50 mg) of the new orally active nonsulfhydryl-converting enzyme inhibitor, ramipril (HOE498), were given to 12 normotensive healthy males, and the pattern of changes in plasma active and inactive renin concentration was evaluated. Active and inactive renin increased after ramipril, and the magnitude of the response was clearly dose related. Active renin rose markedly by 4 hours and tended to decrease thereafter, although remaining higher than basal at 24 hours. In contrast, inactive renin rose more slowly, and the increase was sustained throughout the 24-hour period. The pattern of these changes is consistent with the hypothesis that circulating inactive renin is a biosynthetic precursor of the active form.