We induced atrioventricular dissociation and initiated ventricular pacing in intact dogs and isolated cat hearts. Left ventricular pressure, its time derivative (dP/dt), and action potentials were recorded. When a test pulse was introduced at varying intervals after a period of steady pacing, an optimum contractile response was obtained at an average interval of 720 msec. A similar optimum interval was obtained after pacing at various frequencies and after paired pulse stimulation but was shortened to 560 msec after infusion of epinephrine. The magnitude of the optimum contractile response increased with an increase in the frequency of prior pacing which was accompanied by an increase in the time the cell membrane was depolarized. The optimum contractile response following paired pulse stimulation was greater than that following regular pacing, with the same number of stimuli per minute and the same time of membrane depolarization. The results are explicable in terms of intracellular calcium ion recirculation with separate compartments for release to and uptake from the contractile proteins. A negative feedback control of Ca2+inflow to the cell by intracellular Ca2+content is postulated to explain the effect of paired pulse stimulation and shortening of action potential duration following an increase in regular pacing frequency.Circ Res 47: 559-567, 1980