5 patients are described who developed severe osteomalacia with spontaneous fractures after 2-4 years on dialysis. Phosphate control, vitamin D2 therapy and parathyroidectomy were ineffective. These individuals showed a hypercalcemic tendency but little histologic or radiographic evidence of osteitis fibrosa. After parathyroidectomy, the hypercalcemic tendency remained and bone biopsy revealed gross osteomalacia. A 6- to 12-month therapeutic trial with 1,25-dihydroxycholecalciferol (1,25[OH]2D3) in 3 did not arrest skeletal deterioration. 4 subsequently developed dialysis encephalopathy. These patients appear to have a unique mineralizing defect unresponsive to 1,25(OH)2D3. This "dialysis osteomalacic syndrome" may result from toxic substances associated with uremia or the hemodialysis regimen.