We examined the involvement of the Na+/Ca2+ exchanger in the automaticity of the pulmonary vein myocardium with a specific inhibitor, SEA0400. Action potentials were recorded from the myocardial layer of isolated guinea-pig pulmonary vein preparations, and Ca 2+ transients were recorded from the cardiomyocytes. Spontaneous electrical activity was observed in 17.7% of the preparations, which was inhibited by either SEA0400 or ryanodine. In quiescent preparations, ouabain induced electrical activity and spontaneous Ca 2+ transients, which were inhibited by SEA0400, as well as ryanodine. These results provide pharmacological evidence that the Na+/Ca2+ exchanger underlies the automaticity of the pulmonary vein myocardium.