STC1, a mammalian homologue of stanniocalcin (STC) which plays a major role in calcium/phosphate homeostasis in fish, has been recently isolated. We have characterized the spatiotemporal distribution of STC1 mRNA and protein during mouse embryonic development generally and osteogenesis specifically. Northern blotting analysis of whole embryos showed that STC1 mRNA is highly and differentially expressed during embryogenesis. By in situ hybridization, STC1 mRNA was detected early in mesenchymal condensations and was then found to be highly expressed in perichondrial cells, periosteal cells, and then osteoblasts during endochondral bone formation. In bones forming by intramembranous ossification, STC1 mRNA was not detected until osteogenic cells appeared. The cellular distribution of STC1 protein closely corresponded to that of its mRNA, but the protein was also detected in hypertrophic chondrocytes. In the MC3T3-E1 osteogenic cell model, STC1 protein and mRNA were detectable throughout proliferation and differentiation stages but levels were relatively higher late during nodule formation/mineralization phases. For comparison, STC1 mRNA was also found in epithelial cells of both embryonic and adult intestine that had not previously been described among tissues responsive to calcium/phosphate transport. These results suggest that STC1 is expressed in a time- and cell-specific manner and may play an autocrine/paracrine role during osteoblast development and bone formation.