Non-anemic macrocytosis is occasionally observed in patients with a history of alcoholism or chronic liver disease. Recently we reported that patients with atrial fibrillation (AF) had larger erythrocytes than normal subjects. In the present study, we examined the temporal changes in hematologic measurements during the development of AF in 88 male patients (chronic AF: 49, paroxysmal AF: 39), and compared alcohol intake among the groups. The mean corpuscular volume of erythrocytes was significantly greater in chronic AF patients, both before (98.1±6.1 (SD) fl p<0.05) and after onset (within 6 months: 98.4±7.1 fl p<0.05; 1 year: 98.6±6.2 fl p<0.01), compared with 300 age-matched male control subjects with sinus rhythm (95.9±3.6 fl). Hematocrit increased significantly with development of AF in both chronic and paroxysmal AF patients (p<0.005). Mean daily alcohol consumption did not differ significantly among the control, chronic AF and paroxysmal AF groups. Our findings indicate that erythrocyte size is already larger in patients with chronic AF before the condition develops.