We evaluated the factors that determine the heart rate response to exercise in 60 patients with atrial fibrillation (25 men and 35 women, with a mean age of 61+/-10 years) who underwent symptom limited cardiopulmonary exercise testing with blood sampling of atrial natriuretic peptide (ANP), 2-dimensional echocardiography and cardiac catheterization. Atrial muscles resected during the Maze operation were examined histologically in 12 patients. The heart rate response to exercise depended on the severity of the atrial organic injury, which was expressed as left atrial diameter, ANP secretion during the maximal exercise testing and the histological findings of atrial tissue. Conversely, we believe that the severity of the atrial injury can be predicted from the heart rate response to exercise in patients with atrial fibrillation.