The aim of this investigation was to examine the distribution of procainamide in the canine heart. Eight anesthetized open-chest dogs received intravenous infusions of 14C-labeled procainamide at 40 μg/kg/min for 4 hr. Just prior to the end of the infusion period, 51Cr-labeled microspheres were injected into he left atrium to measure regional myocardial blood flow. The heart was then excised and dissected into regional myocardial sections from each cardiac chamber. Samples from each section were combusted, and the liberated 14CO2 was trapped and counted to determine regional myocardial procainamide concentration. The remainder of each section was analyzed for 51Cr to determine regional myocardial blood flow. Plasma procainamide concentration (mean ± SE) at the termination of the infusion was 2.68 ± 0.14 μg/ml. Left ventricular procainamide concentration was 6.09 ± 0.46 μg/g. The right ventricular drug concentration was 94% (NS), the left atrial concentration was 85% (p < 0.005), and the right atrial concentration was 79% (p 0.005) of the left ventricular concentration. Within the myocardium of each cardiac chamber there was no correlation between drug concentration and blood flow. We conclude that these concentration differences are insufficient to explain differences in procainamide efficacy between ventricular and atrial arrhythmias.