The innervation of three embryologically distinct segments of the canine inferior vena cava was investigated. These segments were termed A (supradiaphragm), B-C (intrahepatic and that between liver and renal veins), and D (infrarenal). Strips were cut from these segments, and their isometric tensions were recorded. Transmural electrical stimulation induced contractile responses in circular strips from segment B-C (66.5% of the maximum norepinephrine-induced response) and in those from D (14.4%), but not in A. These responses almost completely disappeared in the presence of phenoxybenzamine. In segment B-C, however, the remaining small contraction was markedly enhanced by neostigmine and abolished by atropine. The same phenomenon was also observed in the contraction remaining after reserpinization. Longitudinal strips from segment C responded similarly. Concentration-response curves of circular strips for acetylcholine were shifted by neostigmine markedly to the left only in segment B-C, while no significant shift occurred in A and D. It was concluded that the adrenergic innervation is remarkably dense in B-C, sparse in D, and probably lacking in A. In addition, a cholinergic excitatory innervation is present in segment B-C.