The purpose of this study was to compare the myocardial oxygen cost of augmented inotropic state produced by ouabain, norepinephrine, or increased heart rate. This problem was examined in dogs using an isovolumically contracting left ventricular preparation. Inotropic state was measured as the maximum observed contractile element velocity at the lowest common level of wall stress (MAX V). Peak left ventricular wall stress was maintained constant in each dog so that it would not influence changes in myocardial oxygen consumption (MVO2). Ouabain (4 X 10(-2) mumoles/Kg.) and norepinephrine (2 X 10(-3) mumoles/Kg./minute) always augmented inotropic state (MAX V) and increased MVO2. The positive slopes of the regression of MVO2 on MAX V for ouabain (45.4 +/- 12.5 microliter/beat/100 Gm./muscle length/sec; mean +/- SEM) and norepinephrine (34.5 +/- 5.6 microliter/beat/100 Gm./muscle length/sec; mean +/- SEM) were not significantly different, indicating that for an equal augmentation of inotropic state, ouabain increases myocardial oxygen demands to the same extent as does norepinephrine. When the results with ouabain or norepinephrine were compared to results obtained by altering heart rate, it was found that increasing inotropic state by these pharmacologic agents is more costly in terms of myocardial energy demands than when inotropic state is enhanced by increasing heart rate.