Studies were performed to determine the chronotropic effect of acetylstrophanthidin during constant infusion through cannulation of the sinus nodal artery. Ten mongrel dogs weighing 13.5 to 18 kg were studied under sodium thiamylal anesthesia. Epicardial atrial and ventricular electrograms were recorded. The sinus nodal artery was cannulated and infused for 20 minutes at a rate of 2 cc/min with a solution containing acetylstrophanthidin, 0.5 microng/cc. Mean results for the group of 10 animals were determined. There was a gradual acceleration of the atrial rate of 45 beats/min after 6 to 8 minutes of infusion. The peak atrial rate of 175 beats/min was achieved by 10 to 12 minutes. This tachycardia persisted for 2 to 4 minutes without atrioventricular block or premature beats. By 12 to 14 minutes, there was a gradual slowing of atrial rate followed by bradycardia, sinus pauses and atrial arrest. Sinus nodal arterial infusion of acetylstrophanthidin produces an initial positive chronotropic effect and, if maintained, a depression of atrial rate and, terminally, atrial arrest. The gradual time course of development and decline of the tachycardia suggests that the "paroxysmal" atrial tachycardia caused by digitalis excess is the result of enhanced pacemaker automatically rather than reentry, and thus is not truly paroxysmal.