The enhanced renal ammoniagenesis that occurs during acidosis may depend on oxidative processes. To determine this, oxygen consumption (Qo2) of renal slices from acidotic rats (medium pH 7.0) and alkalotic rats (medium pH 7.8) in the presence of 4 different substrates (glutamine, lactate, acetate and 2-oxoglutarate) was investigated. Incremental addition of any oxidizable substrate tested to the incubation medium increased Qo2 until a maximal rate was approached (approximately 17-58% above baseline). Comparing acidotic to alkalotic slices, Qo2 was significantly less at low concentrations of lactate and acetate before maximal Qo2 occurred. In contrast, Qo2 was relatively higher at low concentrations of 2-oxoglutarate and glutamine with acidotic compared to alkalotic slices. Accordingly, acid-base perturbations produce different patterns of Qo2 depending on the substrate and its concentration. These observations coupled with others are consistent with the hypothesis that a relative block in the oxidation of lactate and acetate during acidosis provides more NAD+ for glutamine oxidation and participates in acidotic regulation of renal glutamine metabolism.