To investigate the recent 150% increase in the reported incidence of ventricular septal defects (VSDs) in the United States, the epidemiology of ventricular septal defects was examined. The apparent incidence of VSDs is highly dependent on case finding methods, and more complete diagnosis and reporting probably account for the increase in reported incidence. Variations in case ascertainment also account for the small differences in incidence in studies from different places. The several known risk factors for VSD, including a family history of congenital heart disease and exposure to certain drugs, infectious agents, and maternal metabolic disturbances, explain few cases. Incidence rates are similar in different races and seasons and are unrelated to maternal age, birth order, sex, and socioeconomic status. VSDs occur naturally in a wide range of mammals and in birds, which also have four-chambered hearts. Despite identical genes and similar prenatal environments, the concordance rate in identical twins is only about 10%. The consistency of incidence among individuals with widely differing genes and environments and the frequency of discordance in identical twins suggest that VSDs often occur as random errors in development, at a frequency largely determined by the complexity of normal cardiac morphogenesis. This hypothesis has two major implications: many VSDs are not preventable and parents need not feel responsible for VSDs in their children.