Summary: In contrast to vascular endothelium, the functional role of endocardial endothelium has been largely underestimated. It has now been demonstrated that selective removal of the endocardial endothelium from isolated heart muscle preparations resulted in reduction of twitch duration and peak twitch tension, but did not significantly alter maximal unloaded velocity of shortening (Vmax). Alternatively, the presence of an intact endocardial endothelium increased peak twitch tension mainly by prolonging twitch duration. In the present study, we have investigated the effect of several hormones normally present in the blood on myocardial performance of isolated cat papillary muscle in the presence and absence of a functional endocardial endothelium. The results can be subdivided into three arbitrary groups: (a) The effect was dependent upon the presence of an intact endocardium. (b) The effect was modulated or could be reversed by the endocardium. (c) The effect revealed the existence of a complex role of the endocardium.