The endothelium modulates vascular tone, vasoreactivity, and permeability in response to agonist-stimulation. Much of the pathophysiology of oxidant-induced vascular injury can be attributed to endothelial cell dysfunction. In the past several years, the effects of oxidant stress on agonist-stimulated Ca2+-channels have been described. More recently, the effects of oxidant stress on several other endothelial membrane-transport systems have been elucidated. It now appears that inhibition of the agonist-stimulated Ca2+ channel is due at least in part to membrane depolarization via oxidant-activation of a Na+-permeable, nonselective cation channel. In this review, the effects of oxidant stress on ion transport through the agonist-stimulated Ca2+ influx channel, Na+ and K+ channels, Na+/K+-ATPase, Ca2+-ATPase, and the Na+/K+/2Cl(-) cotransporter are discussed. The interrelated effects of oxidant stress on these endothelial. membrane transport pathways are considered, and the net effect on Ca2+ signaling is described.