The electrophysiologic effects of adenosine, ATP (adenosinetriphosphate), and 18 related compounds were studied in 40 open-chest, anesthetized dogs by direct perfusion of the AV (atrioventricular) junctional region through its nutrient arteries. ATP (1 to 10 mg. per milliliter) produced an immediate heart block lasting 5 to 30 seconds. Adenosine was less effective and no other nucleoside had any significant dromotropic activity. All nucleotides tested (except GTP [guanosine-5′-triphosphate, trisodium pentahydrate] and cyclic GMP [guanosine-3′,5′-cyclic monophosphoric acid]) impaired AV conduction. Transient ectopic beats of AV junctional origin were consistently observed at the onset of AV block produced by ATP. Therefore, chronotropic response of an escape AV junctional rhythm was studied after selective suppression of the sinus node with eserine. ATP and adenosine, each at 10 μg per milliliter, produced exclusively negative chronotropic action. The negative dromotropic effect thus required approximately 1,000 times the concentration which produced a negative chronotropic action. In the absence of any demonstrable positive chronotropic effects from ATP or related compounds, the premature beats are most likely re-entry phenomena due to transient, longitudinal dissociation prior to complete AV block. The demonstration of these direct effects by adenosine and ATP on AV junctional automaticity and conduction may be useful in understanding the pathogenesis of certain arrhythmias and conduction disturbances occurring during myocardial ischemia. © 1972.