A model has been presented here for vitamin D-dependent Ca transport, based on observations of the intestinal Ca absorption process. In this model of vitamin D-dependent Ca transport, processes that occur in different areas of the intestinal epithelial cell combine to result in active transport of Ca2+ from the intestinal lumen to the bloodstream. At the brush-border membrane, 1,25(OH)2D3 causes a rapid opening of Ca2+ channels and transport of Ca2+ into the cell in a matter of seconds to minutes by a process that is independent of gene transcription. Inside the cell, 1,25(OH)2D3 stimulates transcription of the CaBP-D9k/28k mRNA and protein in 1 or more hours after 1,25(OH)2D3 treatment. The CaBP-D9k/28k has greater affinity for Ca2+ than do the brush-border membrane components, so Ca2+ movement through the cytosol is facilitated, with Ca2+ carried by CaBP-D9k/28k. At the BLM, 1,25(OH)2D3 causes an increase in concentration of the PMCA, and stimulates Ca(2+)-pumping activity. The PMCA has still greater affinity for Ca2+ than does the CaBP-D9k/28k. The combination of these vitamin D-dependent events results in active transport of Ca across the intestinal epithelia. Vitamin D sufficiency is necessary for this response to vitamin D treatment. This model may apply to renal DT cells as well as to intestinal absorptive cells. Vitamin D-regulated factors that are involved in vitamin D-dependent active Ca transport and are present in both renal DT and intestinal epithelial cells include VDR, CaBP-D9k/28k and the PMCA. The PMCA is localized to the BLM in both cell types. Both kidney and intestine respond similarly to changes in vitamin D, Ca, or P status. The many similarities between renal DT cells and intestinal epithelia strongly support the application of this model for vitamin D-dependent Ca transport in both tissues.