Both endocardial endothelium and coronary vascular endothelium in the heart influence myocardial contraction by releasing diffusible agents that affect the subjacent myocardium. This effect of cardiac endothelium can be demonstrated both in isolated tissue preparations as well as pump function in intact hearts both in vitro and in vivo. Agents released by endocardial endothelium include both nitric oxide (NO) and an unidentified ‘contraction-prolonging substance’ (‘endocardin’) that respectively decrease and increase the duration of twitch contraction, probably by altering myofibrillar calcium sensitivity. The endothelium of the coronary vasculature also releases NO, with similar effects on contraction, and in addition releases several other unidentified agents. The potential physiological and pathophysiological roles of all of these agents have yet to be fully elucidated and are an important and expanding new area of cardiovascular research that could lead to novel therapeutic possibilities.