It has recently been found that endothelial cells exhibit an unusual change in cellular behavior in response to contact with fibrin. The possible implications of this finding with regard to the mechanism of atherogenesis are discussed. It is proposed that mural fibrin in vivo may produce a disorganized endothelium which can act as a nidus for further fibrin deposition and platelet aggregation. In the presence of inadequate fibrinolysis, a prolonged endothelial lesion could occur which may eventually result in atheromatous plaque formation. This view of atherogenesis requires reduced fibrinolytic activity as a prerequisite for plaque formation, a requirement which is in agreement with currently known data associating atherogenic risk factors with inhibited fibrinolysis.