Regulation by vitamin D(3) of expression of the genes for stanniocalcins 1 and 2 (STC-1 and STC-2) was studied and their levels were shown to be oppositely regulated in the kidney and to remain unaffected in the ovary. Female rats were treated with calcitriol, the active form of vitamin D(3), and alterations in the levels of STC-1 and STC-2 mRNA were determined by Northern blot analysis in the kidney and ovary where the STC-1-expressing cells have previously been identified by in situ hybridization histochemistry. In the kidney, calcitriol treatment increased the STC-1 mRNA levels more than 3-fold, but decreased the STC-2 message to trace levels. In the ovary, however, both STC-1 and STC-2 mRNA levels were not significantly affected by the calcitriol treatment. These results support the hypotheses that (1) STC-1 and STC-2 have opposite effects on calcium and phosphate homeostasis, namely anti-hypercalcemic and anti-hypocalcemic actions, respectively, and (2) the mammalian stanniocalcin system acquired, in addition to the role in the systemic mineral metabolism, a role in the reproduction system that operates independently of the systemic condition.