OBJECTIVE: To investigate the effects of two doses of vitamin D given over 1 year on bone density in ambulatory patients on long-term antiepileptic drug (AED) therapy. METHODS: We conducted two parallel, randomized, controlled trials in 72 adults (18 to 54 years old) and 78 children and adolescents (10 to 18 years) on long-term AED therapy. They received either low-dose vitamin D 400 IU/day or high-dose vitamin D 4,000 IU/day (adults) and 2,000 IU/day (children/adolescents). Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry. RESULTS: In adults, baseline BMD was lower than that of age- and gender-matched controls vs either a Western or an ethnically identical population. After 1 year, there were significant increases in BMD at all skeletal sites compared to baseline in the high-, but not in the low-dose treatment group. However, BMD at 1 year remained below normal. In children, baseline BMD was normal vs age- and gender-matched controls and showed significant and comparable increases in both treatment groups. CONCLUSIONS: In ambulatory adults on antiepileptic drugs, high-dose vitamin D therapy substantially increased bone mineral density at several skeletal sites. In children, both doses resulted in comparable increases in bone mass.