Patients with the third and fourth pharyngeal pouch syndrome, thymic and parathyroid aplasia or hypoplasia, have a very high incidence of aortic arch anomalies and congenital heart disease. These patients present with a unique syndrome characterized by profound hypocalcemia, defective thymic-mediated cellular immune function, and cardiovascular anomalies. The cardiac abnormalities most frequently are conotruncal malformations of the tetralogy of Fallot or truncus arteriosus types and are often the cause of death. Patients with profound neonatal hypocalcemia should be screened for evidence of normal thymic function and congenital heart disease.