We report our observations in a 54-year-old woman with right midseptal AV accessory pathway (AP) and manifest ventricular preexcitation. Although the patient has a several-year history of paroxysmal palpitations, her major daily symptom was impaired exercise tolerance due to resting and exertional dyspnea. Organic diseases of the pulmonary vessels, lung, and heart were excluded by x-ray film and computed tomographic angiography. Cardiopulmonary exercise test prior to ablation showed objective evidence of exertional dyspnea. Stress echocardiography using tissue Doppler imaging revealed significant interventricular asynchrony. The patient underwent successful AP radiofrequency (RF) ablation, which resulted in immediate disappearance of her exertional dyspnea. Cardiopulmonary exercise test performed 1 week after ablation showed significant improvement in pulmonary and cardiac performance. However, within 2 weeks of the procedure, her symptoms of resting and exertional dyspnea recurred simultaneously with recurrence of ventricular preexcitation. Cardiopulmonary exercise capacity in cardiopulmonary exercise test deteriorated as well. After a second RF ablation, the patient's symptoms and preexcitation resolved, and tissue Doppler imaging was free of interventricular asynchrony. These findings suggest that in patients without organic heart and pulmonary diseases, ventricular preexcitation may lead to symptomatic exertional dyspnea in sinus rhythm and interventricular asynchrony that persists during exercise. RF ablation can reverse dyspnea associated with preexcitation. Therefore, in symptomatic patients, preexcitation-related exertional dyspnea during sinus rhythm can be diagnosed by cardiopulmonary exercise test and could be an additional indication for RF ablation in patients with Wolff-Parkinson-White pattern.