To investigate frequency dependent conduction slowing by mexiletine in the human atrium, we examined inter-atrial conduction time (IACT) at different stimulation frequencies (100/min to 220/min) in 13 patients with paroxysmal atrial fibrillation (Paf) and 7 patients without Paf. IACT was prolonged as the stimulation frequency was increased, and either before or after mexiletine administration IACT was longer in the Paf group (max 114 +/- 9 msec, p < 0.01, mean +/- SD) at any stimulation frequency than in the non-Paf group (max 100 +/- 8 msec). The change in IACT induced by mexiletine administration (% delta IACT) was larger in the Paf group (max 14.8 +/- 5.4%, p < 0.05) than in the non-Paf group (max 5.5 +/- 2.2%) at stimulation frequency over 140/min. Effective refractory period measured at the high right atrium was slightly decreased due to mexiletine in both the non-Paf and the Paf group. In conclusion, mexiletine showed frequency dependent suppression of conduction in the human atrial myocardium especially in patients with Paf.