The mechanisms of human atrial fibrillation (AF) are poorly understood. Experimental studies have demonstrated that cholinergic AF in the sheep heart is maintained by high-frequency reentrant sources (drivers) that result in a consistent left-to-right frequency gradient. More recently, clinical studies have confirmed the existence of a hierarchical organization in the rate of activation of different regions in the atria of patients with paroxysmal and chronic AF. Although maximal dominant-frequency sites were found to play a crucial role in the maintenance of AF in some patients, whether AF drivers in humans are focal or reentrant and whether changes in driver activity alter spatial frequency gradients are unclear. To test the hypothesis that localized functional reentry maintains AF in humans, we determined the effects of adenosine infusion on local dominant frequency at different sites of both atria. In patients with paroxysmal AF, adenosine infusion increases local dominant frequencies, particularly at the pulmonary vein-left atrial junction region, amplifying a left-to-right frequency gradient. In patients with chronic AF, dominant frequency is significantly higher than in patients with paroxysmal AF in all atrial regions surveyed, with the highest adenosine increase of frequencies outside the pulmonary vein region. Adenosine-induced driver acceleration is strongly suggestive of a reentrant mechanism in both groups of AF patients.