The ability to excrete an acid load was compared in normal and pyelonephritic rats and correlated with the histochemically-determined level of the following enzymes: Glutaminase I, glutamic dehydrogenase, carbonic anhydrase, NADH diaphorase, NADPH diaphorase, and ATPase. Ammonia excretion at all levels of acid intake up to 10 mEq/day was equivalent in both groups of animals. In the normal animals adaptive increases in activity of glutaminase I, glutamic dehydrogenase, NADH diaphorase and NADPH diaphorase were seen after acid loading. The pyelonephritic animals differed primarily in that diminished activity of glutaminase I was demonstrable on both neutral and acid-ash diets. Tubules caught within scars showed a significant reduction in activity of all enzymes. The results suggest that an intrinsic disease process (i.e., pyelonephritis) may be capable of decreasing the ability of certain enzymes to adapt to physiologic stimuli. In the present study model, however, the diminution in activity of glutaminase I appeared insufficient to limit ammonia production.