• To evaluate the effects of calcitriol (1,25-dihydroxyvitamin D3) therapy for the bone disease induced by long-term treatment with anticonvulsants, we reviewed the medical records of 330 institutionalized oligophrenic children and young adults under 26 years of age to identify the 144 children who required anticonvulsant therapy. Of this latter group, 52 children were found to have serum alkaline phosphatase levels elevated more than 2 SDs above normal and were enrolled into this prospective three-year study. To achieve rapid resolution of the bone disease, we elected to use calcitriol at 0.25 to 0.75 μg/d. After 1195 patient-months of treatment, our data suggest that the dystrophic process was reversed in 42.3% of the cases, as judged by decreases in serum alkaline phosphatase levels at six months, 65.4% of cases at 12 months, and 83.3% of cases at 13 to 18 months. By 30 months of follow-up, all patients showed significant lowering of serum alkaline phosphatase levels. The improvements were slow and gradual. Twenty-six patients in the treatment series of 52 patients initially showed signs of rickets or osteomalacia on roentgenograms of the wrists. Of these 26 patients, 12 (46%) showed improvement on roentgenograms within 24 months of the beginning of treatment. With reference to complications, hypercalcemia (calcium level, >11 mg/dL [2.74 mmol/L]) was encountered at the rate of one episode per 44 patient-months of treatment. Our results strongly suggest that calcitriol is effective in healing anticonvulsant-related osteomalacia among children and youths, with a low incidence of complications.