The adenosine antagonist 8-phenyltheophylline (8-PT) is a diuretic in normal rats and can ameliorate glycerol-induced acute renal failure (ARF) in this species. To define which action of 8-PT is important in its salutary effect in ARF, we have compared its effects with those of enprofylline (a xanthine with little affinity for adenosine receptors) and with those of the tubular diuretic hydrochlorothiazide. In one series of experiments, groups of rats with ARF of 24 h duration were given a single dose of drug or vehicle. Only 8-PT enhanced urine volume when compared with the vehicle-treated group. In a second set of experiments, groups of glycerol-injected rats received drug or vehicle treatment (i.p.) twice daily for 2 days. Rats which received a course of 8-PT treatment had significantly lower plasma urea and creatinine concentrations, a higher glomerular filtration rate, a lower kidney weight and improved kidney morphology when compared with vehicle-treated rats. The only beneficial effect noted after enprofylline treatment was an improved kidney morphology. Hydrochlorothiazide treatment compared with vehicle treatment did not ameliorate any index of renal function but resulted in significant elevations in plasma urea and creatinine levels. The inability of enprofylline or hydrochlorothiazide to mimic the effects of 8-PT in ARF indicate that the effects of 8-PT are probably associated with adenosine receptor blockade and not with a tubular diuretic action.