Atrial septal defect is one of the most common congenital cardiac defects, occurring in 9% to 15% of live births. This defect has been reported to have a genetic etiology in some cases, although the full extent of genetic involvement in atrial septal defect is not known. Because symptoms are often lacking in childhood and manifest primarily in adulthood and because physical findings may be lacking, it is important to take a family history in patients in whom the defect is suspected. When evaluating children, a family history of atrial septal defect should raise suspicion of increased risk so that early diagnosis and treatment can be made. The author reports a cluster of 11 diagnosed atrial septal defects within one 32-member family group, 6 of whom required surgery to repair the defects. It is significant that most of the individuals were lacking in objective findings on physical examination, notably a murmur, as well as in subjective complaints. Diagnoses were made by use of two-dimensional echocardiography with color-enhanced Doppler ultrasonography in all but two cases--one diagnosed with transesophageal echocardiography and one, serendipitously, during cardiac catheterization. Echocardiography also revealed mitral valve prolapse, thin atrial septal wall, with aneurysm in some cases, and regurgitation of mitral or tricuspid valves in several individuals. Cardiac enlargement, usually of the right atrium, was seen in most of the individuals.