The serum concentrations of calcium, phosphorus, parathyroid hormone, vitamin D3 metabolites and their transport protein (DBP) were measured in 18 patients with the nephrotic syndrome (mean daily proteinuria 8.8 g). The glomerular filtration rate was normal in 13 patients while the remaining 5 had a mild degree of renal failure. The serum concentrations of total protein, albumin and DBP were significantly decreased in patients with the nephrotic syndrome. The serum calcium concentration was decreased but the calculated ionized calcium concentration remained normal. The serum concentrations of 25-hydroxycholecalciferol (5.3 +/- 3.1 micrograms/l) and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3 (20 +/- 12 ng/l)] were significantly lower in patients with the nephrotic syndrome and normal glomerular filtration rates than in normal controls (14.4 +/- 4 micrograms/l and 42 +/- 13 ng/l, respectively). The free 1,25-(OH)2D3 index was also significantly below normal (0.9 +/- 0.4 vs. 1.8 +/- 0.4). Total and free 1,25-(OH)2D3 were still further reduced in patients with mild renal failure. The nephrotic syndrome thus results in mild vitamin D depletion with decreased free 1,25-(OH)2D3 concentrations but generally without secondary hyperparathyroidism.