Elevated levels of calcitonin in serum were found in 14 of 48 members studied from two kindreds with familial medullary thyroid carcinoma. Thirteen of these individuals have subsequently been operated on and the presence of the malignancy confirmed, in seven before it was detectable by other examinations. Serum calcitonin determinations are a valuable screening procedure for diagnosis and follow-up studies after operation. The degree of elevation of this polypeptide in the serum appears to correlate with the extent of disease. Since hyperplasia of parathyroids often develops in association with familial medullary thyroid carcinoma, and parathyroid tumors (present in four patients in this study) may occur, the parathyroid glands should be evaluated at operation and grossly abnormal glands removed.