A myothermal/mechanical analysis on non-failing and failing human hearts and normal and pressure overloaded rabbit hearts is reported. Heat production is partitioned into tension-dependent and tension-independent components together with force measurements to provide information about calcium and cross-bridge cycling. In the non-failing human heart the cross-bridge force-time integral is 0·51±0·06 (ns). This value is increased to 0·97±009 (P−1. -beat−1. In the failing preparations calcium cycling is reduced to 16·7± 1·72 nmoles. g−1. -beat−1. In pressure-overloaded hypertrophied, as compared with control rabbit hearts, the calcium cycled per beat is reduced from 43·0±7·3 to 17·6±3·4 nmoles. g−1. It is suggested that the alterations in cross-bridge cycling are more likely to be related to isoenzyme shifts in light chains or troponin T than to myosin isoforms. The calcium cycling changes are well correlated with changes in the sarcoplasmic reticular and sarcolemmal calcium transport proteins. The alterations in the contractile and excitation contractions coupling systems contribute to the functional changes observed in the failing human and pressure-overload rabbit hearts.