Quantitative histology was performed on serial iliac crest biopsies obtained from 14 children with terminal renal failure. A long-term study on the comparative effects of vitamin D2 and 25-hydroxycholecalciferol [25-(OH)D3], in five patients with severe lesions of osteomalacia and/or osteitis fibrosa, demonstrated the efficiency of 25 to 200 mug/day of 25-(OH)D3 and the lack of therapeutic action of 345 to 685 mug/day of vitamin D2. In nine subjects with normal roentgenograms or minimal skeletal alterations, the first biopsy taken at the beginning of intermittent hemodialysis showed evidence of defective mineralization and/or lesions of resorption. Four of these children were treated with 25-(OH)D3 (25 to 50 mug/day) and calcium supplementation orally (0.5 to 1.5 g/day); five children received calcium orally (0.5 to 0.75 g/day) alone. Aggravation of bone lesions during intermittent hemodialysis was observed in patients treated with calcium supplements alone. In subjects who were given 25-(OH)D3, mineralization improved and marrow fibrosis disappeared. However, as the two groups of patients were different in composition and in the manner in which they were treated, it is difficult to state whether the beneficial effects observed were solely attributable to 25-(OH)D3 administration. 25-(OH)D3 therapy induced severe intoxication in two patients. A rise in plasma calcium concentration to 11.0 to 11.5 mg/100 ml was observed in two other patients. It is concluded that: a) pharmacologic doses of 25-(OH)D3 are highly effective in healing bone lesions of children with terminal renal failure; b) such treatment requires strict clinical surveillance as 25-(OH)D3 intoxication may occur even in anephric patients.