Atrial septal aneurysms have been related (either by association or as potential causes) to systolic clicks, atrial arrhythmias, systemic and pulmonary embolism, atrioventricular valve prolapse and atrial septal defect. To study these associations and the incidence of atrial septal aneurysm, we reviewed 80 consecutive patients (female to male ratio 1.9:1, mean age 47 years, range 1 day to 89 years) who had been identified prospectively as having an atrial septal aneurysm. These were found in 36,200 two-dimensional echocardiographic studies (incidence: 0.22% overall; 0.29% in the last year of the study done between 1978 and 1984). Three types of fossa ovalis aneurysm and one type of aneurysm involving the entire atrial septum were observed; a fossa ovalis aneurysm with leftward projection and excursion of less than 5 mm or an aneurysm involving the entire atrial septum with rightward projection was not observed. Atrial septal aneurysm occurred more often as an isolated abnormality than in association with other cardiac malformations, although all patients with an aneurysm involving the entire atrial septum had complex congenital cardiac anomalies of the hypoplastic right heart type. The reported associations between atrial septal aneurysms and atrial septal defect, atrioventricular valve prolapse, midsystolic clicks, atrial arrhythmias and cerebral ischemic events were examined. A hypothesis based on interatrial pressure gradients is proposed to explain the different motions and configurational characteristics of fossa ovalis aneurysms observed in these patients. All patients in whom atrial septal aneurysm is demonstrated should undergo examination for atrial septal defect. Atrial septal aneurysm should be specifically looked for in patients who have these associations and who undergo two-dimensional echocardiography, especially if these abnormalities are unexplained.