Patients with medullary thyroid carcinoma may show two histochemically different populations of non-follicular cells in those parts of the thyroid parenchyma as are not involved by the neoplasm. Besides cells with characteristics consistent with C-cells (basic dye metachromasia and argyrophilia), there is a second, topographically and morphologically distinct population of extra-follicular cells which show argentaffin and orthochromatic cytoplasmic granules. These cells were found in 13 out of 25 cases of medullary carcinoma and they were also present in parathyroid glands in 5 out of 8 of these patients. Their malignant counterparts in the tumours were found in 20 out of 34 cases. Argentaffin and orthochromatic cells were only sporadically seen in a series consisting of various benign thyroid diseases and they were totally absent in cases of malignant neoplasms other than medullary carcinoma. The nature of the argentaffin (orthochromatic) cell is enigmatic. It may be related to the C-cell, but its characteristic morphology and topography suggest that it is a distinct type of cell with different functions.