MC903, a new vitamin D analog has been shown to exert potent effects on cell proliferation and differentiation, while in vivo a decreased activity on calcium metabolism has been observed. In the osteoblast-like cell line UMR-106, MC903 displaces tritiated 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) from its receptor at least as efficiently as 1,25-(OH)2D3. The effect of MC903 on 1,25-(OH)2D3 receptor up-regulation in UMR-106 cells and on bone resorption in fetal mouse radii/ulnae was comparable to that of 1,25-(OH)2D3. MC903 was about 50% less effective in inducing 24-hydroxylase activity and the subsequent C24-side chain oxidation of 25-(OH)D3 compared to 1,25-(OH)2D3. Ketoconazole did not potentiate MC903-induced 1,25-(OH)2D3 receptor up-regulation as was found with 1,25-(OH)2D3 which suggests that the C24-oxidation plays a minor role in the inactivation of MC903. Nevertheless, the comparable effects of MC903 and 1,25-(OH)2D3 on in vitro bone resorption indicate that the lower effectivity of MC903 on bone calcium mobilization in vivo has to be due to a higher metabolic clearance rate.