IntroductionChronic metabolic acidosis results in metabolic bone disease, calcium nephrolithiasis, and growth retardation. The pathogenesis of each of these sequelae is poorly understood in humans. We therefore investigated the effects ofchronic extrarenal metabolic acidosis on the regulation of 1,25-(OH)2D, parathyroid hormone, calcium, and phosphate metabolism in normal humans. Chronic extrarenal metabolic acidosis was induced by administering two different doses of NH4CI 12.1 (low dose) and impaired conversion of 25-(OH)D to 1,25-(OH)2D ( 15).However, the results of measurements of serum 1,25-(OH)2D concentration during experimentally induced metabolic acidosis have not been consistent: reported values have ranged from increased to unchanged to decreased mean concentrations (15)(16)(17)(18)(19). These inconsistencies may have been due in part to the experimental difficulties in controlling acidosisinduced alterations in the plasma concentrations of known modulators of 1,25-(OH)2D production: phosphate (20-22), calcium (23), and parathyroid hormone (23,24