Patients with the nephrotic syndrome and normalrenal function have low levels of 25(OH)D in serum presumablydue to the loss of this metabolite in the urine. Osteomalaciaand hyperparathyroidism have been recently reported to occuras a consequence of those low levels of 25-hydroxyvitamin D(25OHD). We studied six patients (aged 26-52yr) with thenephrotic syndrome (mean duration, 6.7 yr; range, 2-12 yr) andnormal renal function, and evaluated their calcium, phosphorus, PTH, and vitamin D metabolite levels. Bone biopsies wereobtained in all patients. The creatinine clearance ranged from83-134 ml/min-1.73 m2 of body surface, serum albumin was 2.65 ± 0.42 (±SD) g/100 ml, and proteinuria ranged from 3.5-3.2 g/24 h. All patients had normal serum magnesium, phosphorus, ionized calcium, and alkaline phosphatase (total and bone fraction), and normal roentgenographic metabolic bone survey.Serum PTH, measured by the carboxy-terminal RIA, was 5.1 ±2.3 μleq/ml (normal, 2-10), serum 25OHD was 8.8 ± 4.0 ng/ml(normal, 15-30), and 1, 25-dihydroxyvitamin D3 was 38 ± 25 pg/ml (normal, 17-58). Serum vitamin D-binding protein was 420 ± 42 μg/ml (normal, 400-800). The histological appearance ofbone biopsies obtained in these patients was not different fromthat in a group of sex- and age-matched controls. Specifically, there was no increase in the volume of osteoid (unmineralizedbone), the percentage of trabecular surface covered by osteoid, or the number of osteoclasts. The cellular rate of mineralizationwas normal in all six patients. Thus, these data indicate thatlow serum levels of 25OHD in patients with the nephroticsyndrome and normal renal function do not necessarily resultin the development of osteomalacia and/or hyperparathyroidism.