Objectives. This study examined the morphologic features and the clinical significance of massive fatty deposits in the atrial septum of the heart. Background. Large deposits of adipose tissue in the atrial septum were first described in 1964 and have been referred to as ''lipomatous hypertrophy'' of the atrial septum. A relation between these fatty deposits and atrial arrhythmias has been suggested. Methods. The thickness of the atrial septum cephalad to the fossa ovalis ranged from 1.5 to 6 cm in 91 patients and was greater-than-or-equal-to 2 cm in 80 patients. This report focuses primarily on the latter 80 patients. Results. The thickness of the atrial septum in the 80 patients correlated with body weight and the thickness of the adipose tissue in the atrioventricular groove and that covering the right ventricle. In 53 patients (67%), one or more of the four major epicardial coronary arteries were narrowed > 75% in cross-sectional area by atherosclerotic plaque. Atrial arrhythmias were present in 31 patients (40%). Patients with larger deposits of fat (atrial septal thickness greater-than-or-equal-to 3 cm) had a higher frequency of atrial arrhythmias (60% vs. 34%, p < 0.01). The atrial septum was significantly thicker in patients with atrial arrhythmia compared with those without atrial arrhythmias (2.9 vs. 2.3 cm, p < 0.01). Of the 28 patients with available electrocardiograms, 20 (71%) showed atrial arrhythmias (nine atrial premature complexes, seven atrial fibrillation, three atrial tachycardia, one ectopic atrial rhythm and one junctional rhythm). Conclusions. Massive fatty deposits in the atrial septum are associated with large deposits of fat elsewhere in the body and other parts of the heart. They are frequently associated with atrial arrhythmias and atherosclerotic coronary artery disease.