We measured cardiac mechanical restitution curves, which describe the time course of recovery of ventricular contractile strength following a steady-state beat. In the first series of experiments, we studied left ventricles that beat isovolumically throughout the experiment, allowing use of dP/dtmax as a reliable index of contractile strength independent of the influence of changing ventricular pre- and afterload. The commencement of mechanical restitution was found to be associated with the onset of electrical diastole; thereafter, contractile strength rose monoexponentially to a plateau that was maintained for test pulse intervals as long as 15 s. The time constant of restitution (typically 245 ms) was independent of priming frequency and ventricular volume. These findings were interpreted in terms of a model of intracellular calcium fluxes within the myocardial cells. In a second series of experiments, we measured mechanical restitution curves from isolated ventricles that ejected against a simulated arterial impedance system. Under this condition, we did not observe the monoexponential time course of mechanical restitution as was measured under isovolumic conditions. The differences between the mechanical restitution curves measured under isovolumic and ejecting conditions were attributed to the influences of changing hemodynamic conditions on dP/dtmax that caused it to be an unreliable index of contractile strength.