A specific and sensitive radioimmunoassay has been developed and used to measure circulating atrial natriuretic peptide (ANP) in normal man and in patients with chronic renal failure. Circulating ANP levels rose with head-down tilt and exercise, and were raised in patients with chronic renal failure in proportion to volume status. This suggests that ANP release is mediated via increased atrial stretch, although other release mechanisms cannot be excluded. Extracts of normal human plasma subjected to reverse phase HPLC showed one major peak of immunoreactivity co-migrating with alpha-human ANP. However, when plasma extracts from patients with renal failure were chromatographed on a similar system, a second later eluting peak of ANP immunoreactivity was observed. This may represent circulating ANP precursors or degradation molecules. Significant arteriovenous differences in plasma ANP concentration were observed in patients with chronic renal failure. Arterial and venous plasma ANP levels decreased slightly after haemodialysis. Plasma ANP concentrations were inversely correlated with haematocrit in these patients.