Acute renal failure (ARF) is a serious complication following cardiac surgery. This first controlled study was undertaken to verify, if Urodilatin (URO) infusion can revert incipient oliguric ARF after cardiac surgery. We conducted a randomized, double blind trial comparing 7 URO (20 ng/kg/min) with 7 placebo patients. Inclusion criterion was oliguria/anuria (< 0.5 ml/kg/hour) refractory to conventional treatment including administration of dopamine and furosemide. No patient in the URO treated group, but 6 patients in the placebo group had to be hemofiltered or hemodialyzed (p < 0.005) during the 7 day treatment period. In the URO group all 7 patients demonstrated a rapid recovery of diuresis after 2 - 8 hours of treatment that persisted throughout the treatment period. In contrast, placebo treated patients remained oliguric. Serum creatinine (SC) decreased in URO treated patients. No adverse effects were observed during URO administration. After termination of URO, 2 patients underwent hemodialysis for elevated blood urea nitrogen (BUN) values. In the postoperative follow-up period of 60 days, 4 out of 7 placebo treated patients died while still on hemodialysis. In contrast, all URO patients survived. URO is an effective drug to reverse oliguric ARF following cardiac surgery. Prolonged renal failure and renal replacement therapy can be avoided.