Calcitonin released from the thyroid gland (thyrocalcitonin, TCT) inhibits parathyroid hormone (PTH)-stimulated bone resorption in tissue culture. This effect can be used to assay TCT-like activity in human serum. Assays were negative in normal subjects, even after a calcium infusion. Assays were often positive after calcium infusion in patients with hypocalcemia. Serum samples from patients with metabolic disorders of bone were usually negative. Serum TCT-like activity was high in five patients with medullary carcinoma of the thyroid. Calcium infusion increased activity in only two of these patients. Infusion of edetate sodium decreased activity, but long-term administration had no effect. In uncomplicated medullary carcinoma serum calcium and phosphate concentrations were normal and serum PTH by immunoassay was minimally elevated.