The possible role of the autonomic nervous system in the development of myocardial sensitization to isoprenaline produced by DOCA-salt pretreatment was evaluated in bilaterally unanaesthetized rats subject to chronic ganglionic blockade with chlorisondamine or hexamethonium and to treatment with 6-hydroxydopamine. Isoprenaline produced ventricular fibrillation and death in rats pretreated for 6 days with DOCA (20 mg pellet, s.c.) and 0.9% saline. The incidence of mortality was dose dependent and was 76.6% with 150 microgram/kg of isoprenaline. Adrenalectomy did not alter the mortality rate. The combination of adrenalectomy with concurrent chronic ganglionic blockade significantly decreased the incidence of mortality and delayed the time of death. In contrast, 6-hydroxydopamine treatment and adrenalectomy did not alter the incidence of mortality nor time of death. No differences in myocardial noradrenaline turnover were detected in rats susceptible and nonsusceptible to death in ventricular fibrillation. We conclude that myocardial sensitization to isoprenaline induced by DOCA-salt requires a neurogenic component, which is not, however, manifested by changes in myocardial noradrenaline turnover.