Vascular endothelial cells produce a variety of substances known to modulate the tone of surrounding smooth muscle, but the initial steps involved in receptor-response coupling are poorly characterized in these cells. Because the stimulated release of endothelium-derived relaxing factor depends on the presence of external calcium, ion channel-mediated calcium influx might represent an essential first link. Furthermore, agonist-induced endothelial cell hyperpolarization has been widely described, although the ion channels involved and the functional significance of this response remain uncertain. A review of the available literature to date concerning voltage-dependent and agonist-activated ionic currents obtained using patch clamp techiques in vascular endothelial cells is presented here. A discussion of the possible functional roles of the underlying ion channels is included.