BACKGROUND Adenosine is an antiarrhythmic agent widely used for the diagnosis and treatment of supraventricular tachyarrhythmias. Bolus administration of adenosine has been associated with transient atrial fibrillation, but the underlying mechanisms have not yet been delineated, due in part to the technical limitations resulting from adenosine's short half-life. In this study, the rapid, repetitive activation of atrial tissue during atrial fibrillation was exploited to yield a nearly continuous estimate of atrial refractoriness, enabling a description of adenosine's action on atrial refractoriness in humans. RESULTS Simultaneous right and left atrial, narrow-spaced, bipolar electrograms were recorded in 15 patients before, during, and after bolus administration of 12 mg of adenosine during atrial fibrillation. By estimating the local cycle length of excitation from the atrial activation frequency, a refractory period index (RPI) of local tissue was obtained. Adenosine dramatically increased the activation frequency from 6.4 +/- 0.7 to 12.2 +/- 12.2 Hz in the right atrium and from 6.1 +/- 0.6 to 8.7 +/- 1.2 Hz in the left atrium, corresponding to a decrease in the RPI from 156 to 82 msec (P < 0.0001) and from 163 to 116 msec (P < 0.0001), respectively. The magnitude of adenosine's effect was greater (47% vs 29% shortening) (P < 0.001) and the duration of adenosine's effect longer (28 vs 19 sec) (P < 0.05) in the right compared to the left atrium. CONCLUSIONS Adenosine, at doses routinely used clinically, produces a transient, but spatially and temporally inhomogeneous, shortening of atrial refractoriness, which may explain the increased propensity toward atrial fibrillation associated with its use.