The renal oxidation rates of glucose and lactate in the dog in vivo, in the dog cortical slice and in the isolated perfused rat kidney were compared. Lactate decarboxylation rate, on a carbon-atom basis, was from 2 to 10 fold greater than that of glucose. In the substrate-limited perfused kidney, glucose replaced only 30-40% of the substrates oxidized in vivo, while lactate replaced up to 80% of the substrates oxidized in vivo. Insulin lack does not account for these differences in the rates of lactate and glucose oxidation. Glucose and lactate support GFR and Na+ reabsorption to approximately the same extent in spite of their different rates of oxidation. Thus Na+ reabsorptive rate: CO2 production rate is not a constant and depends on the substrate being oxidized. The virtual absence of glucose oxidation by the dog cortical slice suggests either that: 1) glucose oxidation supports primarily medullary Na+ reabsorption while lactate oxidation supports cortical Na+ reabsorption as well of 2) glucose oxidation is more selectively coupled to Na+ reabsorptive work than is lactate oxidation.