The post insult administration of vascular decongestants has resulted in attenuation of experimental acute renal failure (ARF) following the introduction of various nephrotoxins including drugs, heavy metals, and endotoxin. In the present, study, the dose-dependent effects of a novel methylxanthine, HWA-138, were studied in the glycerol-induced murine model of ARF. Renal function, assessed by serial inulin clearances at 24 and 48 h after glycerol injection, urinary electrolyte excretion rates, and renal morphology, was compared between controls and those given glycerol and single i.v. doses of0.1, 0.5, 1.0, 5.0, and 10.0mg/kg of HWA-138, or physiologic saline. Whereas significant renal dysfunction was found in all animal groups given glycerol, the mean inulin clearance values of animals given HWA-138 1 mg/kg closely approximated values found in control rats. There were no changes in renal electrolyte excretion rates in animals given HWA-138 compared with relative natriuresis found in untreated glycerol ARF rat. Although a modest decrease in medullary congestion was associated with rats given 1 mg/kg of HWA-138, there was no obvious structural improvement found with HWA-138. The present data provide further evidence of the potential of methylxanthines in the glycerol-ARF murine model.