Atrial fibrillation (AF) is the most common clinical arrhythmia and a major risk factor for stroke. To investigate the role of genetic factors in a typical clinical population, we determined the extent of familial aggregation in patients with lone AF. To estimate the relative risk to family members, the prevalence of AF for each class of relative was compared to the prevalence in the comparable age and sex group from the general population. Family members had an increased relative risk of AF compared to the general population (risk ratio; 95% confidence intervals): sons (8.1; 2.0-32), daughters (9.5; 1.3-67), brothers (70; 47-102), sisters (34; 14-80), mothers (4.0; 2.5-6.5) and fathers (2.0; 1.2-3.6). Relatives of probands with lone AF are at a substantially increased risk of developing this arrhythmia suggesting a Mendelian genetic contribution to the etiology of this common trait.