To investigate the association between medullary carcinoma of the thyroid (MCT) and carcinoembryonic antigen (CEA), we assayed 78 sera from patients with thyroid diseases for CEA, employing the radioimmunoassay of double antibody technique. All 13 sera from patients with MCT had high levels of CEA, ranging from 14 to 170 ng/ml. Increased serum CEA was noted even in cases of small, localized carcinoma. By contrast, serum CEA levels were normal (below 10 ng/ml) in all other histological types of thyroid carcinoma (33 cases), except for one case of papillary adenocarcinoma. In 32 patients with non-malignant thyroid diseases, with few exceptions serum CEA levels remained within the normal range. The elevated serum levels of CEA in MCT returned to normal after successful operation. Furthermore, very high tissue concentrations of CEA were demonstrated in MCT. The results indicate that CEA is actively produced by MCT, and that its measurement is useful in the diagnosis and management of the disease. It is suggested that the highly specific association of CEA with MCT may well be related to a defect of neural crest origin.