The purpose of this study was to determine whether adenosine or the adenosine deaminase-resistant analogue, N6-R-1-phenyl-2-propyladenosine (RPIA), could slow the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 25) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Intracoronary infusions of adenosine, 10(-7) to 10(-5) M, did not alter the rate of ventricular tachycardia. Ventricular tachycardia slowed by 4.6% with adenosine, 10(-4) M. RPIA, 10(-6) to 10(-4) M, produced a concentration-dependent decrease in the rate of ventricular tachycardia when injected into the left anterior descending coronary artery. This effect of RPIA was reversed by the adenosine antagonist aminophylline, 10(-5) M. After bilateral stellate ganglionectomy, RPIA, 10(-5) M, did not, but metoprolol, 0.5 mg, did slow ventricular tachycardia after intracoronary injection. However, RPIA, 10(-5) M, produced a 43% decrease in the increment in ventricular tachycardia occurring during sympathetic neural stimulation. Therefore, when injected into the left anterior descending artery, adenosine, 10(-4) M, and RPIA, 10(-6) to 10(-4) M, decrease the rate of ventricular tachycardia in 24 hour old myocardial infarction. Furthermore, this decrease in the rate of ventricular tachycardia is the result of prejunctional sympathetic antagonism.