The effects of long-term hypophosphatemia were studied in 10 renal transplant recipients with persistent hypophosphatemia. The renal transplant recipients are 3-14 years (mean 8.7 +/- 4 years) post transplantation. The mean (+/- SD) serum calcium, phosphate, and creatinine levels are 9.66 +/- 0.42, 2.29 +/- 0.16, and 1.47 +/- 0.23 mg/dl, respectively. Carboxy (C)-terminal parathyroid hormone (PTH) is elevated in 8 hypophosphatemic renal transplant recipients. The mean 1,25-dihydroxycholecalciferol [1,25(OH)2D3] level is 33 +/- 20 pg/ml (normal 19-55 pg/ml) compared to 42 +/- 0.6 pg/ml (NS) in 4 normophosphatemic renal transplant recipients with comparable renal function. The 1,25(OH)2D3 level correlates with C-PTH (p less than 0.01) but not serum phosphate. Anterior iliac crest bone biopsies were obtained in all 10 hypophosphatemic renal transplant recipients. Histomorphometric analysis of osteoblastic osteoid, total surface osteoid, bone-osteoclast interface, total resorption, osteoclasts/mm2, osteoid seam width, and relative osteoid volume are not significantly different from normals. Trabecular bone volume is decreased (15.6 +/- 5.7 vs. 23 +/- 5%, p less than 0.01). Comparison of dynamic parameters with normal reveals no differences in appositional and bone formation rate. In summary, in hypophosphatemic renal transplant recipients: hypophosphatemia does not produce osteomalacia; hyperparathyroidism is often observed, and plasma 1,25(OH)2D3 levels, in general, remain in the normal range.