In freshly isolated rat large peripheral arteries and bovine abdominal aorta rings, the effect of L-glutamine on the endothelium-dependent relaxations meditiated by the release of endothelium-derived relaxing factor (EDRF) was studied. The incubation of rat aorta, common carotid and superior mesenteric artery rings with 10(-3) mol/l of L-glutamine (contact time 45 min) produced no changes in their relaxant responses to acetylcholine and histamine. The exposure of bovine abdominal aorta rings to the action of 3 x 10(-4) mol/l of L-glutamine also did not alter their relaxant response to acetylcholine. Higher concentrations of L-glutamine than those used, reduced in parallel the control papaverine-induced and acetylcholine- or histamine induced relaxations. It was concluded that L-glutamine does not inhibit the endothelium-dependent relaxations mediated by the release of EDRF in freshly isolated rat large peripheral arteries and bovine abdominal aorta. The present experiments provide evidence that in these arteries the inhibitory effect of L-glutamine on the release of EDRF cannot be exerted when the endothelium is sufficient in L-arginine and when it does not synthesize L-arginine de novo.