The electrophysiologic effects of adenosine triphosphate (ATP) and adenosine and the modification of these effects by atropine, propranolol, vagotomy, dipyridamole and aminophylline were studied in a canine model. Both ATP and adenosine exerted transient, dose-dependent negative chronotropic and dromotropic effects on the sinoatrial and atrioventricular nodes, respectively. At all doses tested, the effects of ATP were more pronounced. Treatment with either atropine or propranolol plus bilateral cervical vagotomy attenuated the effects of ATP but not of adenosine. In the presence of propranolol plus vagotomy, both the negative chronotropic and dromotropic effects of ATP and adenosine were enhanced and attenuated in a similar manner by dipyridamole and aminophylline. Thus, when ATP and adenosine are injected rapidly into the right atrium of the intact canine heart, vagal involvement in the mechanism of action of ATP but not of adenosine is mainly responsible for the difference in the magnitude of the electrophysiologic effects of these 2 compounds, and only a small part of the electrophysiologic effects of ATP are the result of its degradation to adenosine.