The immediate goal of this research proposal is to investigate critically the side chain metabolism of both 1, 25- dihydroxyvitamin D3 (1, 25 (OH)2D3) and 25-hydroxyvitamin D3 (25-OH-D3) in the rat with a long term goal to understand the physiological significance of side chain metabolism of vitamin D in general. The factors, regulating the production of 1,25 (OH)2D3 in the kidney have been well studied. However, as the circulating as well as the tissue levels of 1, 25(OH)2D3 depend not only on its production but also on its further metabolism, it is vital to understand thoroughly the target tissue metabolism of 1, 25 (OH)2D3 before we embark on investigating the various factors that regulate the target tissue metabolism of 1, 25 (OH)2D3. In vitamin D intoxication, the serum level of 25(OH)D3 can be very high and it appears the toxic effects of vitamin D3 in hypervitaminosis D can be due to high circulating levels of 25(OH)D3. Therefore, understanding of the inactivation pathways of 25(OH)D3 becomes important especially in hypervitaminosis D. Thus, the proposed studies designed to understand the side chain metabolism of both 1,25(OH)2D3 and 25(OH)D3 using the techniques of the isolated perfused rat kidney and liver systems should fill some of the gaps that still exist in our present understanding of the further metabolism of both 1,25(OH)2D3 and 25(OH)D3. This information may also influence our future research into the understanding of the pathogenesis of some of the disease states where there is disturbed vitamin D metabolism.