We studied the acute renal metabolic response in rats made acidotic by a single oral dose of ammonium chloride. Cortical slices from acutely (2-h) acidotic rats utilized more glutamine and produced more ammonia and glucose from glutamine than slices from normal animals. When cortical slices from normal rats were pretreated in vitro with plasma isolated from acutely acidotic rats, they achieved similar increases in glutamine utilization, ammonia formation, and gluconeogenesis from glutamine. We did not observe such stimulation in normal cortical slices pretreated in a low pH-low bicarbonate medium. Our data show that a nondialysable factor is present in plasma from acutely acidotic rats that may be responsible for the early increase in the urinary ammonia observed in such animals.