Members of the Transient Receptor Potential (TRP) superfamily of cation channels are expressed by vascular smooth muscle cells, endothelial cells, and periarterial nerves. However, the functional significance of these channels in the vasculature is just beginning to be revealed. Members of the canonical TRPC subfamily contribute to calcium influx mechanisms triggered by depletion of vascular calcium stores or following receptor (adrenergic, purinergic) activation in vascular smooth muscle. In cerebral artery myocytes, receptor ligands activate TRPC3 channels. In these cells, receptor-mediated Ca²⁺ entry occurs via direct permeation through the TRPC3 channels and also via voltage-dependent Ca²⁺ channels (VDCC); the smooth muscle VDCC are activated by TRPC3 channel-mediated cation influx which depolarizes the smooth muscle cell membrane (Reading et al. 2005). In systemic arteries, TRPC3 channels in smooth muscle are tonically active and contribute to resting membrane potential. TRPC6 channels appear to be receptor-coupled in the peripheral vasculature. The Ca²⁺-activated TRP channel, TRPM4, is a member of the melastatin TRP subfamily and is present in vascular cells. TRPM4 plays an essential role in pressure-induced, smooth muscle cell depolarization, and development of myogenic tone in vitro. Increased intravascular pressure activates TRPM4 channels, which depolarizes the smooth muscle cells, increases VDCC Ca²⁺ influx and triggers myogenic tone (Earley et al. 2004). Cerebral blood flow measurements in vivo indicate that TRPM4 channels contribute to blood flow autoregulation via this myogenic mechanism. Protein Kinase C, which is activated by increased intravascular pressure, enhances TRPM4 activity in vascular smooth muscle cells by increasing the Ca²⁺ sensitivity of the channel. TRP channels of the vanilloid receptor subfamily (TRPV) also play important roles in vasomotor regulation. TRPV4 is present in endothelial and vascular smooth muscle cells and contributes to the endothelial response to vasodilator stimuli as well as the smooth muscle cell response to epoxyeicosatrienoic acids (EETs), which are one type of endothelium-derived hyperpolarizing factor. EETs activate TRPV4 channels. Direct Ca²⁺ entry through the activated TRPV4 channels induces Ca²⁺ release from the sarcoplasmic reticulum in the form of Ca²⁺ sparks; the increased Ca²⁺ spark frequency enhances the activity of BKCa channels, which hyperpolarizes and relaxes smooth muscle cells (Earley et al. 2005). The observations described above indicate that TRP channels play unique and important roles in control of tone in resistance arteries. Ongoing experiments are directed towards further understanding of the mechanisms by which TRP channels in the brain and the peripheral circulation are regulated.