About 80% of the energy derived from the oxidation of substrates is stored in the form of ATP in sufficiently oxygenated hearts. This is reflected by a free energy and chemical potential respectively, of ATP of about 60 kJ/mol. This energy level does not need to be correlated with tissue ATP content and can also be reached with markedly lower amount of tissue ATP. With graded hypoxia, this energy level drops to 50 to 40 kJ/mol without a corresponding reduction in tissue ATP, but with a concomitant fall in peak systolic pressure. Various energy-dependent processes may be responsible for this impairment of cardiac performance. According to experiments with reduced energy demand of the sarcolemmal ion pumping processes and inotropic interventions, the reduced chemical potential of ATP still seems to be sufficiently above that required for the sarcolemmal ion pumping and for the chemo-mechanical energy transformation of the actomyosin system. In contrast, the reduced chemical potential of ATP seems to be no longer sufficient to meet the high level required for normal Ca++ accumulation in the sarcoplasmic reticulum.