Although the biologically active metabolite of vitamin D, 1,25-dihydroxycholecalciferol, is synthesized exclusively by kidney tissue, severe hypercalcemia developed in an anephric child treated with large doses of vitamin D. Treatment by calcium-free peritoneal dialysis acutely reduced serum calcium from 17.2 to 14.2 mg/100 ml. This decrement was effected by removal of three times the total calcium in extracellular fluid, suggesting enhanced bone resorption. Oral prednisolone for 7 days reduced serum calcium to 13 mg/100 ml, but hypercalcemia recurred rapidly after prednisolone was stopped. Calcitonin, given for only 4 one-half days, produced normocalcemia. Maximum serum 25-hydroxyvitamin D (25-OHD), observed immediately after vitamin D was stopped, was 635 ng/ml (normal range 23-32 ng/ml) and subsequently decreased with an initial half-time of 10 days. Losses in peritoneal dialysate may have contributed to disappearance of serum 25-OHD. Because of the high serum levels of 25-OHD and absence of renal tissue, 25-OHD was the likely metabolite that caused hypercalcemia, probably by stimulation of bone resorption, though contribution to hypercalcemia by another vitamin D metabolite cannot be absolutely excluded.