Renal tubular sodium and water handling determined by the lithium clearance technique, plasma concentrations of atrial natriuretic peptide (ANP), angiotensin II, aldosterone, arginine vasopressin (AVP), and urinary excretion of prostaglandin E2 (PGE2) were determined both during basal conditions and before and after intravenous sodium loading with a 2.5% sodium chloride solution in patients with polycystic kidney disease (PKD), ten with normal or slightly reduced kidney function (PKDN) and seven with moderately reduced kidney function (PKDR), and in 15 healthy controls. In PKDN tubular function was normal, whereas in PKDR both proximal and distal reabsorption of sodium and water were reduced. Angiotensin II and aldosterone were normal in both groups of patients. During basal conditions ANP was higher in PKDR than in PKDN. PGE2 was significantly higher in PKDR than in PKDN. For all patients significant correlations were found between GFR and both ANP (rho = -0.51, n = 17, P less than 0.05) and PGE2 (rho = -0.53, n = 17, P less than 0.05). It is concluded that renal sodium handling is normal in the early stages of PKD. With deterioration of kidney function both proximal and distal tubular reabsorption of sodium is reduced and the accompanying changes in ANP and PGE2 may be compensatory phenomena counteracting declining glomerular filtration rate.