Hypercalcemia, rather than hypocalcemia, has been observed in conjunction with severe magnesium (Mg) depletion in rat, in contrast to the development of hypocalcemia in Mg deficiency in various animal models. In the present study, a possible involvement of parathyroid hormone (PTH) in the development of hypercalcemia in rat was studied by using a newly-developed sensitive and specific radioimmunoassay system for the determination of rat PTH. In normal rat model, hypercalcemia occurred in association with a decrease of serum phosphate levels in Mg deficiency. However, serum PTH levels were not suppressed despite the occurrence of hypercalcemia, suggesting PTH as an important factor for the development of hypercalcemia. Of interest, in 5/6-nephrectomized uremic model, hypocalcemia, rather than hypercalcemia, was observed in Mg-deficient rats. Serum PTH levels seemed to be higher, but not statistically significant probably due to a small number of rats. However, infusion study clearly demonstrated that PTH secretion was significantly increased in Mg-deficient uremic rats compared with Mg-replete counterparts. The reason for an increase of serum PTH responses might be explained by Mg depletion itself in addition to a fall in serum Ca levels, because infusion study revealed that the magnitude of the stimulation of PTH secretion was increased in Mg deficiency despite the similar degrees of changes in serum Ca levels and that the set point for the suppression of PTH secretion by Ca might be altered in Mg deficiency. Taken these data together, it was strongly suggested that Mg depletion might enhance PTH secretion in rat.