1. CGP 38 560 A, a low-molecular-weight, non-peptidic renin inhibitor, was well tolerated upon intravenous and oral administration to recumbent healthy volunteers on an unrestricted-sodium diet. 2. After intravenous infusion over 30 min at a rate of 100 ml h-1, doses of 50, 125 and 250 micrograms kg-1 appear to induce a long-lasting inhibition of plasma renin activity. Plasma angiotensin II was decreased in a dose-dependent manner during the infusion and thereafter reverted to the initial level. A concomitant dose-related increase in active plasma renin was observed. Blood pressure was unaffected. The plasma levels of CGP 38 560 reached during infusion were at least 2000-fold higher than the theoretical inhibitory concentration based on in vitro results. 3. After oral administration in doses of 50, 100 and 200 mg CGP 38 560 A, inhibition of plasma renin activity was observed, but plasma active renin was unchanged. Blood pressure also remained unaffected. 4. CGP 38 560 was rapidly cleared from plasma with a half-life of 7.6 min for the first phase and 63 min for the second phase. Plasma levels were 100-fold lower after oral administration than after infusion, indicating a low degree of absorption (less than 1% oral bioavailability).