Only moderately reduced serum 1,25-dihydroxyvitamin D [1,25(OH)2D3] levels were found in 13 hypoparathyroid patients and in 1 pseudohypoparathyroid patient, indicating that factors other than parathyroid hormone are able to mediate the basal production of 1,25(OH)2D3. A significant correlation was found between the levels of circulating 25-hydroxyvitamin D (25OHD) and 1,25(OH)2D, suggesting that a high concentration of 25OHD was able to increase the renal production of 1,25(OH)2D, whereas hypocalcemia and changes in serum phosphate became less important in the present situation. The serum 25OHD and 1,25(OH)2D concentrations were followed during the change of treatment from ergocalciferol to 1 alpha-hydroxycholecalciferol (1 alpha-OHD3). A biological half-life of 3 weeks could be estimated for the plasma 25OHD. The increase in serum 1,25(OH)2D correlated with the dose of 1 alpha-OHD3 given, whereas no correlation was found between the serum calcium level and the 1,25(OH)2D concentration. Unexpected increases and decreases in serum calcium were observed at the same dose of 1 alpha-OHD3 in the same patient and at serum 1,25(OH)2D concentrations within the physiological range.