We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and suggested that CNP might be a local regulator of vascular tone and growth. To evaluate the biological actions of CNP as compared with human atrial natriuretic peptide (hANP), we intravenously administered synthetic CNP (0.43 nmol/kg) and alpha-hANP (0.43 and 0.043 nmol/kg) to healthy humans. The experiments were done on different days in the same five healthy volunteers (31+/-1 yr old). CNP injection caused a transient but significant decrease in both systolic and diastolic blood pressure (-4.3+/-1.3, -4.1+/-1.0 mmHg) with a significant increase in heart rate (+7.6+/-2.6 bpm), and exerted significant diuretic and natriuretic activities (+130+/-80%, +160+/-100% over the basal level). These effects of CNP (0.43 nmol/kg) were comparable to, or less than, those of alpha-hANP (0.043 nmol/kg). CNP injection also significantly suppressed aldosterone secretion (22% reduction as compared with the basal level). Our results demonstrate that intravenously-administered CNP acts as a natriuretic peptide with less potency than ANP.