Summary The doses of ouabain needed to produce cardiac arrhythmia and death were studied in urethan anaesthetized, spontaneously breathing rabbits pretreated with clonidine (6 mg/Kg), triamterene (5 mg/Kg), and amiloride (5 mg/Kg). Plasma kinetics of ouabain infusion as well as plasma and heart concentrations at the time of death were evaluated. No significant differences have been found in animal pretreated with triamterene and amiloride as compared to control animals. The pretreatment with clonidine led to a rise of arrhythmia-producing dose and of plasma concentration of ouabain at the onset of arrhythmias. The lethal dose, the plasma and heart concentrations at the time of death were higher in animals pretreated with clonidine than in controls, but only the difference in left ventricle concentrations was statistically significant. The value of the lethal dose could be influenced by the respiratory disturbance caused by pretreatment with clonidine as far as we can infer from the prolonged interval between the terminal apnoea and cardiac standstill in these animals in comparison with the controls. The higher ouabain plasma concentrations at the onset of arrhythmias and the higher heart ouabain levels at the time of the death in rabbits pretreated with clonidine indicate that the hearts in these animals are more resistent to ouabain and that the protective effect of clondine against ouabain arrhythmiaa is not due to decreased ouabain concentrations or to a decrease of heart uptake of the glycoside.