The clinical usefulness of 25-hydroxycholecalciferol (calcifediol, 25-HCC) was determined in three patients with vitamin D-resistant rickets (familial x-linked recessive in two, and familial autosomal dominant in one). Two patients responded favorably to calcifediol (4,000 to 5,000 units/day) by the following criteria: They showed a net retention of calcium and phosphorus. Gastrointestinal absorption of calcium increased. Urinary excretion of phosphorus and the endogenous phosphorus clearance decreased. In one patient (with familial hypophosphatemia) serum phosphorus concentration and alkaline phosphatase activity returned towards normal; urinary total hydroxyproline increased and nondialyzable hydroxyproline decreased. The third patient (with familial hypophosphatemia) responded to calcifediol during the first 16 days of treatment with increases in serum phosphorus concentration and in urinary calcium excretion. However, he became resistant to calcifediol as treatment was continued.