Twenty-five-hydroxycholecalciferol (25-HCC) is believed to be the biologically active metabolite of vitamin D3 circulating in the blood. Its clinical usefulness was determined in four patients with hypoparathyroidism, three of whom were resistant to vitamin D. Two patients with Vitamin D resistance responded to 25-HCC (5,000 units or less per day) with a significant increase in serum calcium concentration and in urinary calcium excretion. A similar response was shown in a patient with idiopathic hypoparathyroidism who was probably not vitamin D-resistant. In all three patients, 25-HCC significantly increased the gastrointestinal absorption of calcium. In one patient, it increased the urinary excretion of hydroxyproline. In a fourth patient, who had shown resistance to dihydrotachysterol and cholecalciferol, 25-HCC did not significantly affect serum calcium concentration. This patient, unlike the rest, had a degree of moderate renal failure.