Long-term exposure (persistent or intermittent) of man and most mammalian species to hypoxia results in the development of pulmonary hypertension. Significant changes in the structure of pulmonary vessels accompany the hypertensive process and include marked thickening of both the media and adventitia with particularly striking fibroproliferative changes observed in adventitia of chronically hypoxic neonatal animals. The cellular and molecular mechanisms contributing to these changes remain unclear. In this context, it is important to note that the adventitial compartment of at least elastic and large muscular arteries includes within its borders a blood supply, the vasa vasorum. This microcirculatory network has traditionally been assigned a passive role in maintaining vessel integrity through supply of oxygen and nutrients to the outer part of the vessel wall. Data1–3 have emerged, however, suggesting that the vasa network may contribute to the initiation and progression of vascular diseases in the systemic circulation, including atherosclerosis, restenosis, and vasculitis. We have reported4 marked neovascularization of the vasa vasorum at all points along the longitudinal axis of the pulmonary circulation in neonatal calves exposed to long-term hypoxia. These observations raise questions as to how this neovascularization occurs and ultimately how this process affects structural remodeling of the pulmonary circulation under hypoxic conditions.