In the Framingham Study 2325 men and 2866 women 30 to 62 years old at entry were followed biennially over 22 years for the development of chronic atrial fibrillation in relation to antecedent cardiovascular disease and risk factors. During surveillance, atrial fibrillation developed in 49 men and 49 women. The incidence rose sharply with age but did not differ significantly between the sexes. Overall, there was a 2.0 per cent chance that the disorder would develop in two decades. Atrial fibrillation usually followed the development of overt cardiovascular disease. Only 18 men and 12 women (31 per cent) had chronic atrial fibrillation in the absence of cardiovascular disease. Cardiac failure and rheumatic heart disease were the most powerful predictive precursors, with relative risks in excess of sixfold. Hypertensive cardiovascular disease was the most common antecedent disease, largely because of its frequency in the general population. Among the risk factors for cardiovascular disease, diabetes and electrocardiographic evidence of left ventricular hypertrophy were related to the occurrence of atrial fibrillation. The development of chronic atrial fibrillation was associated with a doubling of overall mortality and of mortality from cardiovascular disease.