Walls of conduit blood vessels are nourished by oxygen diffusion from luminal blood and vasa vasorum. The vasa vasorum form a network of microvessels in the adventitia and outer media of conduit blood vessels. Obstruction of flow through vasa vasorum is implicated in the pathogenesis of certain cardiovascular diseases. However, there is no direct evidence of the mechanisms that regulate vasa vasorum tone. Immunohistochemistry was used to study structure of arterial vasa vasorum isolated from porcine thoracic aorta. Tension and perfusion myography were used to directly investigate their reactivity and comparisons were made with other arteries of similar calibre. Vasa consist of layers of smooth muscle oriented around a layer of endothelium and are innervated by nerves, predominantly sympathetic in origin. Vasa are sensitive to constrictors but the reactivity is different from the host vessel, the aorta, and other porcine small blood vessels. Whilst endothelin-1 (ET-1) produces potent contractions, vasa are relatively insensitive to noradrenaline (NA), thromboxane A2 (TXA2) mimetic or angiotensin II. ET-1, at low concentrations, potentiates contractions to NA but not TXA2 mimetic. Low concentrations of K+ potentiate responses to either constrictor. Vasa develop modest myogenic tone, which is considerably less than that in other resistance arteries. Vasa are sensitive to vasodilators bradykinin (BK), substance P (SP) and calcitonin gene-related peptide (CGRP). The endothelium is critical in mediating responses to BK and SP but not to CGRP. Vasa vasorum consist of an entire vascular bed within conduit blood vessel walls that regulate tone in response to constrictors or dilators. Relative insensitivity to constrictors and pressure reflects the function of vasa vasorum and may allow vessel patency. The finding that the endothelium is obligatory in dilator responses and that sensitivity to constrictors can be altered has implications for conduit blood vessels in diseases involving endothelium dysfunction or depolarisation of smooth muscle.