A comparison has been made of the factors concerned with the response of canine and human saphenous veins to adrenergic stimulation. Both vessels have prejunctional muscarinic and beta-adrenergic receptors. When activated by appropriate agonists these receptors decrease and increase the output, respectively, of norepinephrine from the nerve endings. Both vessels have postjunctional alpha 1 and alpha 2 adrenoceptors and postjunctional beta adrenoceptors. Activation of the former two receptors leads to contraction of the smooth muscle, and of the latter to relaxation. There are, however, qualitative differences. In the human veins the responsiveness of the prejunctional beta adrenoceptors exceeds that of the postjunctional, whereas the reverse is true in the dog. As a consequence, in the human vein beta-adrenergic agonists augment, and in the canine veins they depress, the contractile response to sympathetic nerve stimulation.