Background The negative chronotropic effect of beta-blocking agents is likely to provide hemodynamic and energetic advantages. However, the negative chronotropic effect on cardiac energetics observed on the initiation of beta-blockade therapy has not been fully elucidated. Methods and Results In 18 patients with hearth failure, left ventricular pressure and volume, external work (EW), myocardial oxygen consumption per beat (total Vo(2)), mechanical efficiency (EW/total Vo(2)), and Vo(2) for nonmechanical work (total Vo(2) - 2 EW) were measured with the use of conductance catheter and Webster catheter at the following three states under control conditions and after beta-blockade (0.15 +/- 0.07 mg/kg propranolol IV) with and without atrial pacing to keep the heart rate at control levels. Heart rate decreased after atrial pacing was stopped. EW decreased during beta-blockade with pacing and returned to the control level after pacing was stopped. Total Vo(2) did not change during beta-blockade with or without pacing, whereas Vo(2) for nonmechanical work increased with pacing and returned to the control level after pacing was stopped, As a result, mechanical efficiency decreased during beta-blockade with pacing and returned to the control level alter pacing was stopped. Conclusions The negative chronotropic effect of a beta-blocking agent may offset the mechanoenergetical deterioration resulting from its negative inotropic effect through a reduction in oxygen expenditure for nonmechanical work. These findings suggest that the negative chronotropic effect is an important aspect of beta-blockade therapy.