A method is described by which it is possible to dissociate initial pressure and volume while keeping the rate and other conditions of the isolated turtle ventricle constant. The effect of such dissociations on the pressure developed in isometrically and auxotonically contracting ventricles was determined by means of a sensitive optically recording manometer. The amplitude, duration, and area bounded by the pressure curve increased with an increase in initial volume regardless of whether the initial pressure was kept constant or changed in the same or opposite direction. Changes in initial pressure, on the other hand, amounting at times to several cms. of saline, were without significant effect on the amplitude, duration, or area bounded by the pressure curve, provided the initial volume was constant. These observations show (1) that initial volume regulates the activity of the ventricle when its distention varies, (2) that initial pressure changes per se, comparable to those encountered in physiological conditions, have no effect on the contraction of the heart or, at most, only an insignificant one.