The increase in blood flow that accompanies the start of contractions (active hyperemia) is a complex phenomenon involving a fast phase in which blood flow increases quickly and then slows or decreases (seek phase) before stabilizing at a flow corresponding to the metabolic rate (matched phase). This pattern of blood flow change involves contributions from a flow-induced increase in flow, a response to short periods of occlusion or partial occlusion due to force generated by the muscle contraction, and metabolism. Even denervated, the vascular bed, which consists of endothelial cells, vascular smooth muscle cells, and an adventitial layer that has significant secretory potential, is able to coordinate the response pattern. Within the vascular wall, communication is possible bidirectionally across the wall and also along the wall in a retrograde or upstream direction. The signals involved, which range from endothelial cell products such as nitric oxide and endothelin to adenosine, a skeletal muscle metabolite, appear to be situation- and time-dependent. In addition to the communication potential within and along the vascular wall, signals from the vascular system are able to exert inotropic effects on mammalian skeletal muscle.