Oral administration of prednisone (30 mg/day for 9 days) to six normal individuals induced a significant rise in the concentration of serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] within 2 days. In four patients with primary hyperparathyroidism a larger increase of 1,25-(OH)-2D was observed within 3 days. In these patients the 1,25-(OH)-2D concentration remained elevated during the whole period of prednisone administration (10 days) whereas in the control group it had returned to basal levels or below after 9 days of prednisone administration. This response appeared dependent upon parathyroid hormone (PTH) as we found no change in the (basally low) 1,25-(OH)2D concentrations in five patients with hypoparathyroidism during 3-4 days of prednisone administration (30 mg/day). In these patients vitamin D medication had been interrupted 3-5 days before the administration of prednisone, whereafter serum calcium was kept between 2.10 and 2.30 mmol/1 by means of calcium infusion. The response of 1,25-(OH)2D to prednisone is best explained by a stimulatory action of glucocorticoids upon PTH secretion or by the induction of increased PTH sensitivity.