Bacterial endocarditis developed in 24 patients during follow-up in the Natural History Study. It occurred significantly more often in patients with ventricular septal defect (1.5/1000 patient-years) and aortic stenosis (1.8/1000 patient-years) than in those with pulmonary stenosis (0.2/1000 patient-years). Complications, especially emboli and aortic regurgitation, occurred in 50% of the patients. Overall mortality was 25%. Incidence rates were significantly greater for males than for females and greater for patients over 20 years of age than for younger patients. Patients who had had ventricular septal defect treated surgically had a lower incidence of endocarditis than non-surgical patients, whereas surgery did not reduce the incidence in patients with aortic stenosis. The estimated risk of contracting bacterial endocarditis prior to 30 years of age in a patient with medically-treated ventricular septal defect is 9.7%; the risk estimate for surgical patients in 2.0%. Although data regarding the use of prophylactic antibiotics were not available for patients in the Natural History Study, these results certainly suggest that continued antibiotic prophylaxis for dental and certain surgical procedures is mandatory for patients with aortic stenosis, even after successful cardiac surgery. It is the authors opinion that prophylaxis is probably less necessary for patients who have pulmonary stenosis, whether surgically treated or not, and for patients with documented complete closure of VSD.