The distribution of carcinoembryonic antigen (CEA) and its relationship to calcitonin in early, localized, and disseminated (virulent) medullary thyroid carcinoma (MTC) have been studied using immunoperoxidase methods. Carcinoembryonic antigen can be demonstrated within C-cells through all stages of progression of MTC. In early disease (C-cell hyperplasia and microscopic carcinoma), CEA, and calcitonin have a similar distribution, being present in virtually every cell. Likewise, calcitonin and CEA have a similar, homogeneous distribution among cells in gross medullary carcinoma confined to the thyroid region. In both primary and metastatic tumors from patients with virulent, disseminated disease there is an inverse relationship between calcitonin and CEA distribution such that CEA expression is retained and frequently present in the greatest amounts in cells which have poor or absent staining for calcitonin, and present in the least amounts where cellular staining for calcitonin is greatest. It is postulated that in MTC expression of CEA (a marker for early epithelial differentiation), in the face of loss of calcitonin (a marker for terminal differentiation/cellular maturity), may reflect a degree of maturation block in tumors from patients with aggressive disease.