CNP (C-type natriuretic peptide) is a vasodilatory peptide produced by vascular endothelium and the human heart with a short half-life. CNP has been identified within the human kidney; however, few results are available on whether the human kidney is a systemic source of CNP. The aim of the present study was to establish whether CNP is secreted by the human kidney and if synthesis is blunted in CHF (chronic heart failure). A total of 20 male subjects (age, 57 ± 2 years; mean ± S.E.M.) undergoing CHF assessment (n = 13) or investigation of paroxysmal supraventricular arrhythmia (normal left ventricular function in sinus rhythm during procedure) (n = 7) were recruited. Renal CNP production was determined from concomitant plasma concentrations in the aorta and renal vein. When considering all subjects, a significant step-up in plasma CNP was found from the aorta to renal vein (3.0 ± 0.3 compared with 8.3 ± 2.4 pg/ml respectively; P = 0.0045). The mean increase in CNP was 5.3 ± 2.4 pg/ml (range, -0.9 to +45.3 pg/ml). In patients with CHF, the aortic concentration was 3.3 ± 0.4 pg/ ml compared with a renal vein concentration of 4.3 ± 0.6 pg/ml (P = 0.11). In those with normal left ventricular function, the respective values were 2.5 ± 0.5 and 15.7 ± 6.0 pg/ml (P = 0.01). In conclusion, CNP is synthesized and secreted into the circulation by the normal human kidney, where it may have paracrine actions. Net renal secretion of CNP appears to be blunted in patients with CHF.