Factors related to atrial natriuretic peptide (α-ANP) regulation and its potential impact on excretory transplant function were examined in a prospective cohort study of 20 patients with end-stage renal disease over 21 days after allogenic kidney transplantation. Depending on posttransplant graft function, patients were separated into those with primary renal function (PF group, n = 10) and posttransplant acute renal failure (ARF group, n = 10). ANP concentrations were markedly elevated in both PF and ARF immediately after renal transplantation, even when compared with the pretransplant dialysis phase (PF group: 939 ± 467 pg/ml; ARF group: 648 ± 306 pg/ml, on 3rd postoperative day; ‘normals’: 72 ± 35 pg/ml). Whilst ANP levels were persistently elevated in patients with acute renal failure, there was a steady decrease in plasma concentrations in patients with primary renal function (PF: 270 ± 122 pg/ml on 21 st day). ANP concentration correlated with endogenous creatinine clearance (rz = 0.56, p < 0.01 PF group). Moreover, there was a greater correlation between ANP levels and postoperative hydration status, measured as central venous pressure or the difference from predialysis dry weight (rz = 0.79 and rz = 0.74, p < 0.01, PF group). Systolic blood pressure was also positively correlated with ANP concentrations. Together, these factors accounted for a total correlation coefficient of r = 0.87 (p < 0.001) in multiple regression analysis. No significant relation was found between plasma ANP levels and total or fractional sodium excretion or free water clearance. With the restoration of renal function most vasoactive hormones (renin-aldosterone system, catecholamines, vasopressin) decreased towards normal values, whilst ANP plasma concentrations remained elevated.