Experiments were conducted to determine the effects of the reduced-size atrial natriuretic factor (ANF) analog, A68828, on renal function in rats with cisplatin (CP)-induced acute renal failure. CP was given as a single intraperitoneal injection (7.5 mg/kg) 3 days before experiments. In separate groups of rats, the renal response to intravenous infusion of A68828 at 3, 10 or 30 μg/kg/min or ANF[1-28] at 0.03, 0.1 or 0.3 μg/kg/min for 2 hr was evaluated. Another group of CP-treated rats were infused with the vehicle (0.1% bovine serum albumin in 0.9% NaCl). CP treatment resulted in a marked decline in glomerular filtration rate(GFR), arterial pressure, heart rate and reabsorption of water and electrolytes compared to untreated control animals. Infusion of A68828 produced a dose-dependent improvement in the glomerular filtration rate. The highest dose of A68828 produced a nearly 3-fold increase in the glomerular filtration rate, whereas arterial pressure was decreased; heart rate was unchanged. Despite producing a significant diuresis and natriuresis, net tubular reabsorption of water and sodium was also increased. Similar dose-dependent effects were observed with the native peptide, ANF[1-28]. These data indicate that infusion of the reduced-sized analog of ANF, A68828, can significantly improve glomerular and tubular function in rats with acute renal failure induced by CP.