Increased 1,25-dihydroxyvitamin D levels and decreased basal and calcium-stimulated calcitonin serum levels have been found in children with Williams-Beuren syndrome (WBS). To determine whether isolated or combined disturbances of secretion or action of the calcium-regulating hormones may cause the tendency to hypercalcemia in WBS, we investigated several aspects of calcium metabolism in 27 normocalcemic children and adults, aged 2 to 47 years, with WBS. With the exception of slightly decreased 25-hydroxyvitamin D and slightly increased calcitonin in serum, all measured basal indexes of calcium and bone metabolism, including the serum levels of intact parathyroid hormone and 1,25-dihydroxyvitamin D, were comparable to control values. Total and extractable calcitonin, the latter representing the monomeric and biologically important form of the hormone, showed the same relative increase after a low-dose calcium infusion in patients and control subjects, indicating a normal capacity of the calcitonin-producing C cells of the thyroid gland in WBS. Furthermore, exogenous parathyroid hormone induced a normal response of 1,25-dihydroxyvitamin D, cyclic adenosine monophosphate, and phosphate excretion, indicating a normal response of the renal 25-hydroxyvitamin D-1 alpha-hydroxylase and the renal receptor-adenylate cyclase system to parathyroid hormone. These findings suggest that neither deficient calcitonin secretion nor increased renal sensitivity to parathyroid hormone is a feature of WBS in normocalcemic patients.