The effect of warming on adrenergic neurotransmission was examined in canine cutaneous veins. Isometric tension was recorded from rings of saphenous veins of the dog in organ chambers filled with physiological salt solution. During contractions caused by potassium or prostaglandin F2 alpha, warming from 37 to 41 degrees C caused an augmentation. During contractions caused by stimulation of the adrenergic nerves, and by exogenous norepinephrine, warming caused a relaxation. The relaxation with warming was not altered by the beta-adrenergic antagonist, propranolol, or by inhibitors of extraneuronal and neuronal uptake of norepinephrine. During contractions evoked by the alpha 2-adrenergic agonists, alpha-methyl norepinephrine and B-HT 920, warming caused a relaxation, whereas during contractions due to the alpha 1-adrenergic agonists, cirazoline , methoxamine, ST 587, and phenylephrine, it caused an augmentation. The relaxation caused by warming during norepinephrine-induced contractions was prevented by the preferential alpha 2-antagonists yohimbine and rauwolscine, but not by the preferential alpha 1-antagonist, prazosin. In strips of saphenous vein incubated with [3H] norepinephrine , warming did not affect the release of labeled transmitter evoked by nerve stimulation. These experiments indicate that warming directly enhances contractility of vascular smooth muscle, while depressing the responsiveness of cutaneous vessels to sympathetic nerve activation by a selective inhibitory effect on postjunctional alpha 2-adrenoceptors. Relaxation with warming is greater during nerve stimulation than during administration of exogenous norepinephrine, which may be due to a predominance of postjunctional alpha 2-adrenoceptors in the neuromuscular junction.