Effects of nicotine and electrical transmural stimulation on isolated dog cerebral arteries were studied. Nicotine (5 × 10<sup>–8</sup>–10<sup>–4</sup> m) usually evoked a phasic contraction in the basilar artery and a relaxation in the middle cerebral artery. The nicotine-induced contraction and relaxation were abolished by pretreatment with pentolinium (10<sup>–5</sup> m) but not by tetrodotoxin (TTX) (10<sup>–7</sup> m). Phentolamine (10<sup>–6</sup> m) or bretylium (10<sup>–5</sup> m) abolished or reversed the nicotine-induced contraction, and partially reduced the nicotine-induced relaxation. Electrical transmural stimulation elicited a phasic contraction in the basilar artery and a relaxation or slight contraction in the middle cerebral artery. The contraction induced by transmural stimulation was abolished by bretylium and TTX, and augmented by phentolmine. The relaxation was not inhibited by bretylium. The uptake of <sup>3</sup>H-norepinephrine (<sup>3</sup>H-NE) by the basilar and middle cerebral arteries was markedly reduced by cocaine (3 × 10<sup>–6</sup> m). Nicotine and transmural stimulation increased the tritium efflux from both arteries. The nicotine-induced increase in tritium efflux was inhibited by pentolinium. The increased efflux induced by transmural stimulation was abolished by TTX, attenuated by bretylium, and augmented by phentolamine. These results indicate that nicotine and transmural stimulation cause both vasoconstrictor and vasodilator effects in the dog cerebral arteries and that the vasoconstriction is mediated through an adrenergic mechanism.