Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP, or ATP) combined with magnesium chloride were infused after an ischemic renal injury. Twenty-four hours later: rats that received no infusion or one of the components of the mixture alone had reduced C(In) (355 ± 40 μl/min/100 g of body wt vs. 977 ± 40 control value), decreased RBF (3550 ± 205 μl/min/100 g of body wt vs. 5095 ± 171 control value), elevated FE(Na) (0.65 ± 0.10% vs. 0.17 ± 0.04 control value), and diminished U(Osm) (862 ± 110 mOsm/kg vs. 1425 ± 132 control value); rats given dopamine or phenoxybenzamine maintained low C(In) (365 ± 50) despite improved RBF (4678 ± 222); rats in fused with either AMP, ADP, or ATP combined with magnesium chloride had markedly improved C(In) (594 ± 44, P < 0.01), increased RBF (4269 ± 223, P < 0.01), normalized FE(Na) (0.18 ± 0.07%, P < 0.01), and improved U(Osm) (1201 ± 106 mOsm/kg, P < 0.05). In animals given no infusion or only magnesium chloride, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and magnesium chloride had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and magnesium chloride had improved C(In) despite ischemic periods of 30, 45, and 60 min; and the degree of improvement was directly related to the quantity of ATP and magnesium chloride administered: The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. The data indicate that adenine nucleotides combined with magnesium chloride when infused after the initiation of acute renal failure significantly improve the C(In) and tubular function and suggest that these agents effectively enhance recovery following an ischemic renal insult.