Presynaptic supersensitivity was demonstrated in isolated rat atria and perfused hearts 2 h after an intravenous injection of 6-hydroxydopamine (6-OH-DA), 100 mg/kg. This coincided with a maximum depletion of cardiac endogenous noradrenaline, a disappearance of the fluorescence of terminal adrenergic nerve fibers in the atrial myocardium, and an abolished chronotropic response to tyramine. The chronotropic response to dopamine was also significantly diminished. Maximal supersensitivity to the chronotropic effect of noradrenaline was observed 72 h after the injection of 6-OH-DA. Two weeks after the administration of 6-OH-DA, supersensitivity to noradrenaline was less marked, and the response to tyramine was restored. These changes corresponded to an increasing noradrenaline content in the heart and to the reappearance of histofluorescent fibers in the atria.