In helical strips of dog distal superficial temporal artery denuded of endothelium and partially contracted with prostaglandin F2α (PGF2α), nicotine produced a moderate relaxation preceded by no contraction or a slight contraction. The contraction was less than that observed in proximal arterial strips obtained from the same dogs and was abolished by α-adrenoceptor antagonists. Relaxations under α-receptor blockade were greater in the distal than in the proximal arteries. Treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, abolished the relaxation caused by nicotine and transmural electrical stimulation (5 Hz for 40 s), the response being reversed by L- but not by D-arginine. In monkey temporal arteries of the distal and proximal portions treated with a-antagonists, nicotine produced similar magnitudes of relaxation, which were abolished by treatment with the NO synthase inhibitor. Vasodilator nerves appear to play an important role in regulation of small arterial tone; noradrenergic vasoconstrictor function is less and vasodilator nerve function is more evident in dog distal arteries than in dog proximal arteries. The neurally induced relaxation in dog and monkey distal temporal arteries is postulated to be mediated by NO derived from nerves.