BACKGROUND Intestinal infusion of leucine augments the maximal gastric-acid secretory response to pentagastrin and serves as a bioassay for intestinal-phase acid secretion. Another action of leucine is to decrease tyrosine flux into neural tissues. We hypothesized that the mechanism of leucine-stimulated acid secretion involves its ability to alter tyrosine absorption. METHODS We administered tyrosine intrajejunally and intravenously to anesthetized, vagotomized rats during maximal pentagastrin stimulation and measured acid output in response to intrajejunal infusion of leucine. RESULTS Intrajejunal tyrosine produced a dose-dependent inhibition of leucine-stimulated acid secretion but only mild effects on acid secretion in response to pentagastrin alone. Intravenous tyrosine infusions also decreased acid secretion in response to intestinal leucine but required much higher doses. CONCLUSIONS Tyrosine exerts a specific inhibitory effect on leucine-stimulated acid secretion, which is mediated intraluminally. Because tyrosine is an important regulator of adrenergic nervous system activity, we speculate that the mechanism of leucine-stimulated acid secretion may involve modulation of the sympathetic nervous system, thereby affecting acid secretion.