It is believed that reciprocating tachycardia and accessory pathways play important roles in atrial fibrillation (AF) in patients with Wolff-Parkinson-White (WPW) syndrome. However, the mechanism by which AF occurs is not yet fully understood. This study was performed to evaluate the contribution of sympathoadrenal activity to the onset of AF in patients with WPW syndrome. Symptom-limited treadmill exercise testing was performed and plasma norepinephrine and epinephrine concentrations were measured simultaneously in 27 patients with WPW syndrome and 20 control subjects. In 13 patients with WPW syndrome and AF, plasma norepinephrine and epinephrine concentrations increased to 3.69±2.44 and 0.76±0.69 ng/ml at maximum exercise, respectively. These values were significantly higher (p<0.001) than those in control subjects and in patients without AF. Pretreatment with 0.2 mg/kg of propranolol significantly reduced the incidence of exercise-induced atrial premature complexes (χ²=7.33, p<0.05). With oral β-blockade for an average of 22.8 months, the incidence of AF decreased significantly from 1.77±0.53/patient per year to 0.33±0.57/patient per year (p<0.001). Augmented sympathoadrenal activity in patients with WPW syndrome may contribute to AF. (Jpn Circ J 1996; 60: 43 - 49)