<jats:p> The mechanism of an increase in metabolic rate induced by lactate was investigated in the toad Bufo marinus. Oxygen consumption (V˙o <jats:sub>2</jats:sub>) was analyzed in fully aerobic animals under hypoxic conditions (7% O<jats:sub>2</jats:sub> in air), accompanied by measurements of catecholamines in the plasma, and was measured in isolated hepatocytes in vitro under normoxia by using specific inhibitors of lactate proton symport [α-cyano-4-hydroxycinnamate (CHC)] and sodium proton exchange (EIPA). The rise in metabolic rate in vivo can be elicited by infusions of hyperosmotic (previous findings) or isosmotic sodium lactate solutions (this study). Despite previous findings of reduced metabolic stimulation under the effect of adrenergic blockers, the increase inV˙o <jats:sub>2</jats:sub> in vivo was not associated with elevated plasma catecholamine levels, suggesting local release and effect. In addition to the possible in vivo effect via catecholamines, lactate induced a rise in V˙o <jats:sub>2</jats:sub> of isolated hepatocytes, depending on the concentration present in a weakly buffered Ringer solution at pH 7.0. No increase was found at higher pH values (7.4 or 7.8) or in HEPES-buffered Ringer solution. Inhibition of the Lac<jats:sup>−</jats:sup>-H<jats:sup>+</jats:sup> transporter with α-CHC or of the Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup> exchanger with EIPA prevented the increase in metabolic rate. We conclude that increasedV˙o <jats:sub>2</jats:sub> at an elevated systemic lactate level may involve catecholamine action, but it is also caused by an increased energy demand of cellular acid-base regulation via stimulation of Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup> exchange and thereby Na<jats:sup>+</jats:sup>-K<jats:sup>+</jats:sup>-ATPase. The effect depends on entry of lactic acid into the cells via lactate proton symport, which is likely favored by low cellular surface pH. We suggest that these energetic costs should also be considered in other physiological phenomena, e.g., when lactate is present during excess, postexerciseV˙o <jats:sub>2</jats:sub>. </jats:p>