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The distribution of C-cells was reviewed in a series of human thyroid glands from 84 autopsies. The C-cells were demonstrated by the Grimelius method modified by De Grandi [10] and immunohistochemically using anticalcitonin by the method of Sternberger et al. [43]. The immunohistochemical method proved to be considerably more useful than the silver reaction. In half the cases C-cells were found symmetrically in both lateral lobes, concentrated around an axis running in a cranial-lateral-dorsal to caudal-medial-ventral direction. In about a quarter of the cases the C-cells were only approximately symmetrical in distribution, and rarely was no symmetry visible in their distribution. A completely homogeneous distribution of C-cells throughout the thyroid was never demonstrated. C-cells are normally concentrated in the upper and the middle thirds of the thyroid, but in cases with hyperplasia they were found predominantly in the middle and lower thirds of the lateral lobes. Exceptionally, some C-cells were present in the isthmic region or no C-cells were found in the entire thyroid at all. Thyroid nodules are generally free of C-cells. The number of C-cells seems to be more or less constant when the thyroid is of normal weight. In large goiters, however, the number of C-cells increases. Since the distribution of C-cells was rather irregular all the cases considered, thyroid biopsies are of little help in generally evaluating their reactive state. This does not apply to C-cell tumors, i.e. medullary carcinoma of the thyroid, where cytologic examination has been proven to be a valuable diagnostic method.