Three adult patients with hypocalcemia secondary to severe magnesium depletion were evaluated in order to determine the etiology of hypocalcemia in this syndrome. In each patient, the concentration of circulating parathyroid hormone was within the range of normal despite severe hypocalcemia and hypomagnesemia. In the 2 patients tested, circulating parathyroid hormone increased transiently above normal in response to treatment with magnesium. Urinary excretion of phosphate and cyclic AMP increased normally in response to an acute infusion of parathyroid extract and serum calcium increased 2 mg/100 ml and 1.4 mg/100 ml, respectively, in response to intramuscular injections of the hormone in the 2 patients who were tested. It was concluded that the normal but inappropriately low concentrations of parathyroid hormone were attributable to hypomagnesemia and could account for the perpetuation but not the onset of hypocalcemia in this syndrome. Peripheral resistance to parathyroid hormone is not operative in the kidney and if present in bone is only partial and can be attributed secondarily to hypocalcemia rather than primarily to hypomagnesemia. It is postulated that hypocalcemia develops initially as a result of decreased heteroionic exchange of calcium for magnesium at the skeletal surface.