The cells of the vascular wall are coupled via gap junctions, which allow exchange of currents and small signal molecules in order to synchronise cell responses. Indeed, local hyperpolarisation of arteriolar or capillary endothelial cells by the stimulator acetylcholine is transmitted via endothelial gap junctions. This results in a rapid, well coordinated dilation within a microvascular network synchronising the changes in vascular tone of local resistance vessels and their upstream feeding vessels which is a prerequisite for increasing the conductance of the vascular network, e.g. during exercise. In addition, there is a local exchange via gap junctions of ions and small molecules between endothelial cells and, in small vessels, between the endothelium and the underlying vascular smooth muscle. One example is the exchange of calcium or calcium-releasing molecules such IP3. Stimulation of cultured endothelial cells with histamine elicits a homogeneous increase of the intracellular free calcium concentration in virtually all cells of a monolayer. However, a higher time resolution reveals that a rapid increase in calcium occurs only in part of the cells giving rise to the spread of a calcium wave over the whole monolayer which is mediated by gap junctional communication. Indeed, pharmacological inhibition of gap junction coupling significantly reduces the number of cells responding to histamine with an increase of calcium which corresponds with the observation that only a part of the endothelial cells expresses the H1-receptor. As a consequence, inhibition of gap junctional communication between endothelial cells leads to a pronounced reduction of the calcium dependent NO production in these cells. Likewise, blockade of GJ also reduces the endothelium-dependent dilation of isolated resistance arteries. Calcium waves induced by mechanical stimulation of a single cell typically propagate over three to four rows of adjacent cells. In the presence of the IP3 receptor blocker Xestospongine the spread of such a calcium wave is restricted to the immediately adjacent cells indicating that the observable spread of the wave is not only due to diffusion of calcium from the stimulated cell. The spread of calcium waves can be modulated by endogenous regulators of gap junctional permeability. We have found that endothelial nitric oxide is such a modulator, acting selectively on Cx37, one of the three connexins (Cx37, Cx40 and Cx43) that form gap junctions in the endothelium. Since Cx37 seems to play a prominent role in the gap junctions of the myoendothelial junctions, NO may control the interaction of endothelial cells in microvessels. The modulation of gap junctional communication and hence, spread of calcium waves is a new mechanism by which the apparent sensitivity of endothelial cells to vasoactive stimuli, such as histamine can be controlled. It remains to be shown whether or not defects in endothelial gap junctional communication contribute to impairment of endothelial function as observed in cardiovascular diseases.