The reactivity to sympathetic nerve activation and the metabolism of 3H-norepinephrine were compared in isolated saphenous veins of dogs and rabbits. The veins of both species were equally sensitive to electrical stimulation, but the magnitude of the contractile responses to such stimulation was larger in the dog. The response to depolarization of the adrenergic nerve endings by high K+ solutions was depressed by phentolamine to a greater extent in the dog than in the rabbit vein. After incubation with 3H-norepinephrine, electrical stimulation caused a greater evoked release of tritiated transmitter in the dog than in the rabbit veins. These experiments suggest that the former are more densely innervated. In resting conditions and during electrical stimulation, the dog veins and the rabbit veins degraded 3H norepinephrine in a different way. In both species, neuronal uptake appeared to be of minor importance in the disposition of 3H-norepinephrine released during continuous electrical stimulation. The reactivity to exogenous catecholamines and acetylcholine were also compared in both veins. The apparent sensitivity to exogenous norepinephrine was greater in rabbit than in dog veins. This difference disappeared after inhibition of neuronal uptake with cocaine, suggesting that it is due to the difference in density of adrenergic innervation. There was no interspecies difference in the sensitivity of the β-adrenoceptors, but the maximal effect of β-adrenergic activation by isoproterenol was larger in the dog than in the rabbit veins. In both species acetylcholine caused inhibition of adrenergic neurotransmission, and direct activation of the venous smooth muscle cells. As regards the latter effect, dog veins were less sensitive to acetylcholine but their response was stronger than that of rabbit veins. These results suggest that the density of adrenergic innervation modulates mainly the apparent sensitivity of the venous smooth muscle to α-adrenergic activati