A historical survey of the growth of ideas about the circulation of the blood and about the endothelium is provided as a background to the specialized papers that follow. Over the years, in the course of clarifying its structure and function, the status of the endothelium has gradually evolved from that of an inert semipermeable barrier that determines the exchange of substances between blood vessels and tissue spaces to that of a specialized organ that is unusual in its dispersion throughout the body as the lining of blood vessels. This unique arrangement has enabled it to play different roles in different parts of the vascular tree and in different organs and to manifest distinctive responses to injury according to its structure and location. As a corollary, because its responsiveness is strongly influenced by its ambience and neighboring tissues, it seems inevitable that extrapolations from function in vitro to function in vivo require considerable prudence.