The effect of aminophylline (theophylline complexed with ethylenediamine) on the severity of glycerol-induced myohemoglobinuric acute renal failure was examined in rats. In the first series of experiments, one group of rats received twice daily injections of aminophylline following the induction of acute renal failure, and a second group (controls) received twice daily injections of saline. Only one of the aminophylline-injected rats but five of the saline-injected rats died during the 3-day follow-up period. Moreover, mean serum creatinine was lower in the aminophylline-injected rats than in the saline-injected controls on each of the 3 days, demonstrating that aminophylline reduced the renal functional impairment. In the second series, single injections of aminophylline were given at the time of glycerol injections or 3, 6, or 24 h later. As assessed by mean serum creatinine during the 3-day follow up, even single injections had protective effects if given during the initiation phase (0-3 h after glycerol). Since aminophylline dissociates into theophylline in biological fluids, and since theophylline is an adenosine-receptor antagonist, these observations are consistent with the hypothesis that adenosine plays a pathogenic role in myohemoglobinuric acute renal failure in rats.