To determine the effects of acute metabolic acidosis and alkalosis on leucine metabolism in vivo, mongrel dogs were infused with [1-14C]leucine for 8 h, along with NaCl, HCI, or NaHCO3 over the last 4 h. Arterial pH did not change from the basal value during NaCl infusion but decreased (P less than .01) and increased (P less than .01) during HCl and NaHCO3 infusions, respectively. Total leucine carbon entry did not change from the basal value during saline infusion but increased (P less than .01) with acidosis and decreased (P less than .05) with alkalosis. Compared with saline controls, acidosis increased (P less than .01) leucine oxidation. During alkalosis decreased (P less than .01) leucine oxidation. During acidosis, total plasma essential and nonessential amino acid concentrations increased (P less than .05), whereas during alkalosis, total plasma essential and nonessential amino acid concentrations decreased (P less than .05). These studies suggest that acute alterations in arterial pH may affect the regulation of protein metabolism in vivo and must be considered in the interpretation of results from experiments in which alterations of acid-base homeostasis may have occurred.