The relationship between plasma angiotensin and the reduction of blood pressure with the angiotensin converting enzyme inhibitor enalapril was studied in rats. Blood pressure was measured in conscious rats with indwelling arterial catheters. To measure angiotensin II, plasma was analyzed by physical separation of angiotensins using high performance liquid chromatography followed by radioimmunoassay. The effects of both single (acute) and long-term (chronic) dosages of enalapril were measured. After a single oral dose of enalapril (10 mg/kg), mean arterial pressure fell from 111 +/- 3 to 86 +/- 3 mm Hg (p less than 0.005). Despite the blood pressure reduction, plasma angiotensin II was unaffected (control, 9.9 +/- 1.8 vs 9.7 +/- 1.1 pg/ml). After a higher single oral dose of enalapril (30 mg/kg), there was a reduction in both mean arterial pressure (81 +/- 5 mm Hg, p less than 0.005) and plasma angiotensin II concentration (2.3 +/- 0.6 pg/ml, p less than 0.01). The chronic effects of converting enzyme inhibition were evaluated in rats given enalapril in their drinking water (30 mg/kg 24 hr) for 1 week or 2 months. Mean arterial pressure remained equally low after chronic administration (for 1 week or 2 months), but plasma angiotensin II increased above normal (after 1 week, 28.9 +/- 8.7, p less than 0.01 vs control; after 2 months, 43.1 +/- 16.2 pg/ml, p less than 0.05 vs control). Although plasma angiotensin converting enzyme activity was undetectable at any time after enalapril administration, there was a partial return of the angiotensin I pressor response with chronic administration. The data are most compatible with actions of converting enzyme inhibitors independent of the blockade of plasma angiotensin II formation.