Neuronal activity increases local blood flow in the central nervous system (CNS), and this increase is the basis of BOLD and PET functional imaging techniques. Capillaries adjacent to active neurons are devoid of smooth muscle, and it is generally assumed that blood flow is regulated by smooth muscle associated with precapillary arterioles. However, most (65%) noradrenergic innervation of the CNS vasculature is of capillaries rather than arterioles (Cohen et al. 1997), and in both skeletal muscle and brain a retrograde vasodilatory signal passes from capillaries located near metabolically active cells to precapillary arterioles (Dietrich et al. 1996; Berg et al. 1997; Iadecola et al. 1997), suggesting that blood flow control signals are initiated at the capillary level. Pericytes, which are apposed to CNS capillaries and contain muscle actin and non-muscle actin and myosin, are potential initiators of such signalling. Using video imaging techniques we have studied the potential for pericytes to regulate the diameter of capillaries on the vitreal surface of the isolated P21 rat retina (animals were humanely killed). Pericytes are labelled by an antibody directed at the membrane chondroitin sulfate proteoglycan NG2, and are separated by a distance of 37.7±3.8 μm (mean±s.e.m, n=24) along retinal capillaries. Electrical stimulation with an electrode touching a pericyte evoked a contraction, which constricted capillaries at localized points. Electrical stimulation of pericytes resulted in an average constriction of 75.3±3.3% (mean±s.e.m, n=22) of the capillary at these points. In some cases constriction propagated to more distant sites of the vessel, close to other pericytes. Stimulation of pericyte-free zones on the capillaries evoked an average constriction of 5.0±4.7% (mean±s.e.m, n=11), which is significantly different to the constriction observed at pericyte sites (p≤0.0001, Student’s t test). Similar changes in capillary diameter were observed following superfusion of retinal capillaries with 100 μM UTP. At sites occupied by pericytes, capillaries constricted by 59.4±8.7, (mean±s.e.m, n=7), suggesting a possible role for purinergic P2 receptors in the control of capillary diameter. These experiments identify pericytes as possible mediators of the vascular response to changes in neural activity at the capillary level, and pericytes could therefore play a key role in CNS disease and its therapy.