In order to evaluate the roles of the renin-angiotensin-aldosterone system and of catecholamines in 117 normotensive patients with chronic congestive heart failure (CHF), a study was made of the relationships between plasma concentrations, hepatic extraction of these humoral factors and hemodynamic parameters. In 6 patients with moderate to severe CHF, the acute effect of oral; administration of angiotensin I converting enzyme inhibitor, SQ 14225 (captopril), on mean arterial pressure (MAP), peripheral venous pressure (VP) and these humoral factors was investigated. In patients with CHF of Class III-IV (according to NYHA classification), the urinary norepinephrine (U-NE) excretion increased. Plasma norepinephrine (P-NE) levels increased in proportion to the severity of CHF (p less than 0.001) and had a positive correlation with systemic vascular resistance (SVR) (p less than 0.01), VP (p less than 0.05), pulmonary artery wedge pressure (PWP) (p less than 0.01) and plasma renin activity (PRA) (p less than 0.01). P-NE correlated negatively with the cardiac index (p less than 0.02). Hepatic extraction of norepinephrine (EX-NE) was reduced in patients with elevated right atrial pressure (RAP) (p less than 0.05) and negatively correlated with VP (p less than 0.05). In patients with elevated P-NE, U-NE increased significantly (p less than 0.01), despite their decreased renal clearance of norepinephrine (CNE) (p less than 0.02). There was no significant difference in EX-NE between these patients and patients with normal P-NE. PRA was higher in Class III-IV patients than in Class I-II patients in the prediuretic period (p less than 0.01). PA showed a significant positive correlation with PRA (p less than 0.001). Hepatic extraction of aldosterone (EX-A) was reduced in patients with elevated RAP (p less than 0.05) and was negatively correlated with VP (p less than 0.05). Following captopril administration, PRA increased consistently and PA decreased. MAP fell, especially in 2 patients with mitral stenosis. The heart rate tended to decrease. VP also fell with symptomatic improvement. The decline in VP was correlated with the decrease in P-NE (p less than 0.01). These findings suggest that the sympathetic nervous system contributes to the elevation of SVR and PWP even before frank heart failure develops. The rise of P-NE seems to be due to increased norepinephrine release from sympathetic nerve beds, whereas a decrease in hepatic extraction and renal clearance probably has only a minor effect. The renin-angiotensin system also seems to contribute to elevation of SVR, to maintain effective arterial pressure by enhanced sympathetic activity, and the renin-angiotensin system seems to be a main determinant of PA in CHF.