Experiments were performed in order to determine the influence of sympathetic denervation on alpha-1 and alpha-2 adrenergic responses in canine saphenous veins. In female dogs anesthetized with sodium pentobarbital, the left lumbar sympathetic chain was excised from L1 to L7. After a 3- to 5-week period, the left (denervated) and right (innervated) saphenous veins were removed, cut into rings and suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Denervation reduced significantly the norepinephrine content of the venous rings and the contractile responses evoked by the indirect sympathomimetic amine, tyramine. The contractile responses evoked by exogenous norepinephrine were augmented by denervation under control conditions (16.7-fold shift in concentration-effect curve) and also after inhibition of neuronal and extraneuronal uptake and beta adrenoceptors (3.8-fold shift in curve). Denervation increased the contractile responses evoked by the alpha-2 adrenergic agonist, UK 14,304 (5-fold shift in concentration-effect curve), but not those produced by the alpha-1 adrenergic agonist, phenylephrine. The selective augmentation of alpha-2 adrenergic responses by denervation may reflect the preferential innervation of alpha-2 adrenoceptors in the canine saphenous vein.