Asian Indians who immigrate to northern Europe have lower serum 25-hydroxyvitamin D [25(OH)D] than Caucasians, and they develop vitamin D deficiency, rickets, and osteomalacia. We investigated vitamin D metabolism, the effects of 25(OH)D3 on vitamin D metabolism and activity of 25(OH) D-24-hydroxylase, the rate-limiting enzyme for degradation of 25(OH)D, from cultured skin fibroblasts of Asian Indians and compared them with cultured skin fibroblasts of Caucasians in the southern United States. Normal subjects, ages 20-40 yr, were admitted to a metabolic ward for 2.5 days and given a daily diet containing 400 mg calcium and 900 mg phosphorus. Serum vitamin D, serum 25(OH)D, urinary calcium, and urinary phosphorus were significantly lower, whereas serum immunoreactive intact parathyroid hormone (PTH) and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] were significantly higher in Asian Indians than in Caucasians. Administration of 25(OH)D3 increased serum 25(OH)D and urinary calcium but did not change serum PTH or serum 1,25(OH)2D in Asian Indians. In cultured skin fibroblasts, Emax and Vmax of 25(OH)D-24-hydroxylase activity were significantly higher in Asian Indians. In summary, in Asian Indians serum vitamin D and 25(OH)D are markedly reduced, altered vitamin D metabolism is only partially reversed by 25(OH)D3, and 25(OH)D-24-hydroxylase activity in cultured skin fibroblasts is markedly increased. Thus, Asian Indians residing in the U.S. are at risk for developing vitamin D deficiency, rickets, and osteomalacia.