Fourteen patients with medullary carcinoma of the thyroid (MCT) and hypercalcitoninemia were studied. Serum concentrations of calcium, phosphorus and iPTH (C-terminal) were normal. Serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels were increased (p less than 0.001) in spite of reduced serum 25-hydroxyvitamin D (25-OHD) levels (p less than 0.02) indicating an enhanced activity of the renal 1 alpha-hydroxylase. Serum 24,25-dihydroxyvitamin D levels were normal and correlated positively with serum 25-OHD. Histomorphometric analyses of iliac crest bone biopsies after in vivo tetracycline double-labelling were performed in patients and controls. The patients showed a normal trabecular bone volume. The mean size of the cortical osteocytic lacunae was increased (p less than 0.001). Significant increases were found in fractional formation surfaces (p less than 0.05), fractional labelled surfaces (p less than 0.01) and fractional resorption surfaces (p less than 0.005) in trabecular bone. The appositional rate of newly mineralized bone was reduced (p less than 0.025). The mean osteoid seam width was normal due to an unchanged mineralization lag time and a normal osteoid appositional rate. The bone formation rate at tissue level was high normal. The altered vitamin D metabolism may be caused by a direct effect of hypercalcitoninemia on the renal l alpha-hydroxylase or may represent an adaptive change in calcium-phosphorus homeostasis. The dynamic bone changes are similar to those found in primary hyperparathyroidism and may be caused by an enhanced sensitivity to circulating PTH induced by the increased 1,25-(OH)2D.