In order to establish the characteristics of net renal transport and utilization of alpha-ketoglutarate (alpha-KG) in the rat, we have precisely quantified the renal blood flow, the urinary flow and the rates of alpha-KG delivery, filtration, reabsorption or secretion, excretion, uptake or production by an in vivo rat kidney preparation. In normal rats, alpha-KG uptake was higher than alpha-KG reabsorption at both endogenous and elevated plasma alpha-KG concentrations; thus, a net peritubular transport, which was the main supplier of alpha-KG to the renal cells, took place. Saturation of reabsorption and peritubular transport of alpha-KG occurred at blood alpha-KG concentrations about 30 and 150 times above normal, respectively. Acute metabolic acidosis was found to have no effect on renal handling of alpha-KG. At endogenous plasma alpha-KG concentrations, alkalosis converted net renal uptake into net renal production of alpha-KG resulting in addition of alpha-KG by the renal cells both to blood and to the luminal fluid. Elevation of blood alpha-KG concentration restored the renal uptake of alpha-KG. This uptake, which was entirely accounted for by the peritubular transport of alpha-KG, reached a maximum which was lower than that observed in normal and acidotic rats.