The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures.