A longitudinal prospective study of 17 normal human kidney donors before and after uninephrectomy revealed changes in mineral metabolism during compensation for loss of renal mass. Increases in carboxy terminal parathyroid hormone (PTH) and urinary cyclic adenosine monophosphate (AMP) occurred at 1 week and persisted for up to 3 years after surgery. 1,25(OH)2D levels fell from 26.5 +/- 2.0 to 18.6 +/- 1.7 pg/mL (P less than 0.05) at 1 week. Tubular reabsorption of phosphate (TRP) fell from 83.4% to 72.3% at 1 month and remained at this level throughout the study. At 6 months, several changes developed that were suggestive of increased PTH effect: hypocalciuria, a decrease in serum phosphate, and the return of 1,25(OH)2D levels to baseline or above. 1,25(OH)2D levels showed an inverse correlation with serum phosphate at 6 months (r = 0.75, P less than 0.005) and 1 year (r = 0.60, P less than 0.01). In addition, at 6 months, an increase in bone mineral content by forearm photon absorptiometry was indirect evidence for a period of positive calcium balance. The compensatory changes demonstrated in this study after loss of renal mass took place over the course of several months and persisted for up to 3 years.