Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study. Autopsy specimens of 17 tumors of the atrioventricular nodal region were studied. Sudden death occurred in 14 children and adults; seven of these patients had a history of atrioventricular block or syncope. Three tumors were incidental findings in infants with other congenital anomalies; diaphragmatic agenesis, pulmonary hypoplasia, and Meckel's diverticulum in one patient; mitral atresia in one; and congenital hydrocephalus, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and patent omphalovitelline duct in the third. Immunohistochemical stains demonstrated strong positivity for carcinoembryonic antigen in 13 of 13 cases, B72.3 antigen in 5 of 7 cases, and cytokeratin in 11 of 11 cases. Twenty control cases of mesothelioma and mesothelial hyperplasia were all negative for B72.3; one showed focal carcinoembryonic antigen staining. Ultrastructural analysis of one case demonstrated short rudimentary microvilli not characteristic of mesothelial cells. We conclude that so-called mesotheliomas of the atrioventricular nodal region are not of mesothelial origin, because of strong carcinoembryonic antigen positivity and occasional positivity with B72.3, as these antibodies react with glycoproteins found in endodermally derived tissue and generally not with mesothelial tissue. Conduction system tumors are most likely congenital rests of endodermal origin, can be associated with other congenital anomalies, and often cause symptoms of heart block and sudden death. 