Urodilatin is a newly identified analogue of human atrial natriuretic factor-(99-126) [ANF-(99-126)], which has recently been isolated from human urine and has 32 amino acid residues [ANF-(95-126)]. To investigate renal and cardiovascular effects in men, eight healthy subjects received injections of 25, 50, and 100 micrograms urodilatin iv compared with 50 micrograms ANF-(99-126) and placebo. Blood pressure decreased (P less than 0.05) after 50 micrograms ANF-(99-126), whereas urodilatin lowered diastolic blood pressure only at the highest dose (P less than 0.01). Heart rate increased (P less than 0.05-0.01) dose dependently after urodilatin injections. Glomerular filtration rate rose after 100 micrograms (from 120 +/- 3 to 156 +/- 7 ml.min-1.1.73 m-2, P less than 0.001) and 50 micrograms urodilatin (from 116 +/- 7 to 149 +/- 13 ml.min-1.1.73 m-2, P less than 0.01) but not after 25 micrograms urodilatin, ANF-(99-126), or placebo. Effective renal plasma flow was not significantly modified. Diuresis and excretion of sodium, chloride, and guanosine 3',5'-cyclic monophosphate increased (P less than 0.001) dose dependently; effects of 25 micrograms urodilatin equaled those of 50 micrograms ANF-(99-126). Plasma renin, aldosterone, and catecholamines were unchanged. We conclude that urodilatin can acutely modify renal and cardiovascular function in men and seems to exert more potent renal effects than ANF-(99-126).