Adenosine triphosphate is effective in terminating re-entrant supraventricular arrhythmias, but previous studies have demonstrated a wide range for therapeutic doses. We determined dose response curves for ATP (Striadyne) in order to determine the mechanism of variability in response to this agent. In addition, this enabled comparison of AV nodal, SA nodal intraventricular and accessory pathway properties. Incremental bolus doses of ATP were administered to patients following electrophysiologic studies. Sinus node effects were determined by the change in spontaneous sinus cycle length (n = 7). AV node response was assessed by measuring the AH interval during atrial pacing at CL 400 msec (n = 7). The effects of intraventricular automaticity were assessed by observing the spontaneous cycle length (n = 1), and accessory pathway effects were observed during atrial or ventricular pacing (n = 2). ATP prolonged sinus cycle length in all patients (delta CL 295 +/- 91 msec) with a mean effective dose of 0.84 mg (range 0.5-8.0 mg). ATP prolonged AH interval with a mean effective concentration of 2.0 mg. The mean dose to produce AV block was 4.6 mg. In contrast, a ventricular escape rhythm failed to show cycle length prolongation but only showed cycle length shortening. The accessory pathways did not demonstrate block even in high doses. Thus, adenosine triphosphate selectively affects the sinoatrial node and AV nodal tissue with inhibitory effects on automaticity and conduction. The effect on intraventricular automaticity was excitatory, with minimal effects observed in accessory pathways.