The two major pathophysiologic mechanisms responsible for the development of secondary hyperparathyroidism (SHPT) in advanced renal insufficiency are phosphorus retention and low levels of 1,25-dihydroxyvitamin D[subscript]3 (1,25-(OH)[subscript]2D[subscript]3].;The actions of the hormonal form of vitamin D extend beyond its role in mineral homeostasis. Recently, analogs of vitamin D that are less calcemic, but retain the therapeutically useful properties of 1,25-(OH)[subscript]2D have been developed;This study was designed to determine if a high phosphorus diet could be the main contributor for increasing plasma phosphate and parathyroid hormone (PTH) and reducing the production of renal 1,25-(OH)[subscript]2D[subscript]3 in renal failure (reduced renal cell mass). Another objective was to determine if vitamin D analogs could be used as an effective drug in lowering plasma PTH and increase calcium during SHPT;One hundred twelve 60-day-old male rats of Harlan-Sprague-Dawley (weighing 400-450 gm) were divided into 7 groups: SLP, SHP, NLP, NHP, NHP-A, NHP-B and NHP-C. SLP and SHP were sham (S) operated groups whereas the rest were unilaterally nephrectomized (N). The rats were fed two synthetic diets with low (LP) or high (HP) phosphorus levels. Three groups of rats: NHP-A, NHP-B, and NHP-C were simultaneously given an oral administration of 18 ng/day of 1,25-(OH)[subscript]2D[subscript]3 (A), 18 ng/day of 1,25-(OH)[subscript]2D[subscript]2 (B) or 2 [mu]g/day of 1,25,28-(OH)[subscript]3D[subscript]2 (C), respectively, every day for 30 days;After 30 days all rats were made unconscious with CO[subscript]2-O[subscript]2 (50%:50% vol/vol) and decapitated. Blood samples were collected and plasma was analyzed for inorganic phosphorus, calcium, 1,25-(OH)[subscript]2D[subscript]3, PTH and creatinine;The results of this study indicate that sham and nephrectomized rats fed high dietary phosphorus lost 9.50 and 24.72%, respectively, of their initial body weights. Plasma phosphate increased significantly as dietary phosphorus increased. The treatment with vitamin D analogs lowered plasma phosphate, PTH and raised plasma calcium and 1,25-(OH)[subscript]2D[subscript]3. Among the vitamin D analogs, 1,25-(OH)[subscript]2D[subscript]3 was found to be superior. These changes indicate that vitamin D analogs may be effective in SHPT.