A pentagastrin stimulation test using a calcitonin (CT) immunoradiometric assay was performed in 38 healthy subjects and in the following 50 patients: 25 subjects from families with at least 2 known cases of medullary thyroid carcinoma (MTC), 11 subjects from families with apparently sporadic MTC, 2 pheochromocytoma carriers, 1 primary hyperparathyroidism, 8 patients with thyroid nodules, and 3 others with various diseases. In healthy volunteers, basal CT values were always less than 10 ng/L; the response to pentagastrin was below 30 ng/L for 36, and for the remaining 2, the peaks reached 30 for 1 subject and 48 ng/L for the other. The pentagastrin-stimulated CT peak was above 30 ng/L in each of the patients presented here, and all were thyroidectomized. In screening the 25 relatives of patients with familial MTC, a CT peak level over 30 ng/L was constantly associated with C-cell disease (23 cases of MTC and 2 of C-cell hyperplasia). A response to pentagastrin above 100 ng/L was observed in 15 patients among the 23 with MTC. In 8 of the 10 patients with a peak CT level between 30-100 ng/L, pathological examination showed a MTC; the other 2 had C-cell hyperplasia and a negative linkage study analysis. In the 25 other patients in the study without familial MTC, the pentagastrin-stimulated CT level was over 100 ng/L in 11 of the 14 subjects with MTC. The abnormal CT response to pentagastrin, which has been used as a criterion for surgical treatment, is currently determined by an immunoradiometric assay. Our study confirms that subjects with a peak CT level above 100 ng/L should undergo surgery whatever the reason for the test. In the context of inherited MTC, our results suggest that for patients with a CT peak level between 30-100 ng/L, surgery may actually be postponed when their probability of being gene carriers is low. Recent progress with the characterization of specific mutations in affected individuals will make familial screening much easier in the next few months.