Electrophysiologic characterization of the onset and termination of atrial fibrillation (AF) is poorly defined. Our study population consisted of 21 consecutive patients (mean age 58 +/- 9 years, 6 women) with intermittent (10 patients) or persistent (11 patients) AF. Mapping of the left atrium (LA) and the right atrium (RA) during initiation and termination of AF was performed with a 64-electrode basket catheter. A total of 92 spontaneous AF onsets (in 16 patients) and 63 spontaneous AF terminations were analyzed. Irrespective of the origin of the triggering atrial premature complex (APC), the onset of AF was preceded by an intermediary rhythm that consisted of repetitive firing from the focus that generated the initial APC, reentry around the mitral annulus, or typical atrial flutter. The earliest fibrillatory activity was constantly produced by circumvented regions (generators) localized most frequently in the posterior wall of the LA. Generators of fibrillatory activity were not observed in the RA for any of the patients. In the RA, AF is maintained by a mixture of macro-reentry and driving wave fronts of left atrial origin. Four modes of AF termination were observed: a multifocal rhythm (19 episodes, 30%), left atrial tachycardia (17 episodes, 27%), direct conversion to sinus rhythm (15 episodes, 24%), and conversion to typical atrial flutter (12 episodes, 19%). A repetitive rapid rhythm initiated most often by APCs plays a crucial role in the initiation of AF via activation of the generators of fibrillatory activity. The LA plays a central role in the initiation of AF by serving as a substrate for generators of fibrillatory activity. Termination of AF consists of a heterogenous group of unstable rhythms.