The endocardial endothelium (EE) has been shown to modulate the contraction of the subjacent myocardium. Selective damage of the EE modifies the twitch of isolated cardiac muscle in a rather unique manner: an immediate and irreversible decrease in twitch duration, i.e., an earlier start of isometric relaxation which is accompanied by a decline in peak twitch tension. This phenomenon has been confirmed in different species and in vivo conditions where impairment of EE caused abbreviation of left ventricular pressure-time curve due to earlier pressure fall. An intact EE enhances myocardial performance by increasing myofilament Ca++ sensitivity. Several substances including atrial natriuretic peptides, α 1-agonists, vasopressin, serotonin and aggregating platelets exert their inotropic action on the myocardium through the EE. The mechanisms of EE modulation of myocardial performance are still under investigation and the possibilities include release of various chemical messengers (NO, prostaglandins and endothelin-1) by the EE and/or the role of EE as a physico-chemical barrier. The EE may play an important role in the compensatory mechanisms in the pathophysiology of various cardiac conditions because of its direct modulation of myocardial performance, as mediator of inotropic actions of a number of plasma hormones and by secretion of growth factors.