The greater cardiac oxygen consumption (VO2) under pressure than under volume load has been accounted for by the greater ventricular wall force under pressure load. We cannot fully agree with this because the wall force has not always been uniquely correlated with VO2. We attempted to account for the greater VO2 under pressure load by the ventricular systolic pressure-volume area (PVA), which we previously showed uniquely correlated with VO2. In isolated supported canine hearts, we produced servo-controlled ejecting contractions the stroke work (SW) of which was doubled from control by doubling ejection pressure (P) with comparable stroke volume (SV) and by doubling Sv with comparable P. Despite comparable increments in SW from 370 to 680 mmHg.ml under two different loads, VO2 and PVA increased significantly more under pressure load (from 0.033 ml O2/beat and 800 mmHg.ml to 0.0560 and 1,800, respectively) than under volume load (increasing to 0.038 and 1,200, respectively; P less than 0.01). These results suggested to us a new mechanism underlying the greater VO2 under pressure load.