To assess hemodynamic and energetic effects of different drug interventions on idiopathic dilated cardiomyopathy (IDCM), we determined hemodynamic variables of myocardial oxygen consumption (MVO2) in 37 patients with IDCM. Hemodynamics were measured during routine left and right heart catheterization. MVO2 was analyzed from myocardial blood flow (measured by the argon method) and aortocoronary sinus blood oxygen difference. The hemodynamic variable which correlated best with MVO2 was shown to be the systolic stress time integral (STI). Four different representative compounds were tested with respect to their acute effects on myocardial energetics (MVO2/STI) in patients with IDCM who were in compensated heart failure (NYHA class II-III). The drug interventions were performed at rest. Intravenous injection of the vasodilator nitroprusside yielded a 35% reduction in STI and a 30% reduction in MVO2; in other words, the ratio MVO2/STI was not altered. Injection of the calcium sensitizer and phosphodiesterase inhibitor pimobendan also did not alter this ratio, as both STI (36%) and MVO2 (33%) were lowered. The profound reduction in STI (60%) seen with the phosphodiesterase inhibitor enoximone was accompanied by a much smaller decrease in MVO2 (19%); therefore, the ratio of MVO2/STI increased significantly. An increase of this ratio was also seen with the partial beta-1 receptor agonist xamoterol. However, in this case STI did not change, whereas MVO2 increased by 26%. In summary, vasodilation has energy-saving effects, whereas positive inotropism is an energy-consuming process. We conclude that the overall effect on myocardial energetics of a drug which possesses both positive inotropic and vasodilating properties depends on the balance of the two properties.