1,25-dihydroxycholecalciferol (1,25 (OH)2 D3) causes dose-dependent inhibition of fibroblast growth and collagen synthesis and has numerous immunoregulatory activities. We assessed the effects of oral 1,25 (OH)2 D3 in the treatment of patients with systemic sclerosis (SS). Eleven patients with SS entered an open prospective study. Oral 1,25(OH)2 D3 was given at a mean dose of 1.75 micrograms/day. The effects of the treatment were evaluated using clinical examination and physical measurements. After the treatment period (6 months to 3 years), a significant improvement, as compared with baseline values, was observed. No serious side-effects were observed. These results suggest that high-dose 1,25 (OH)2 D3 may be a useful therapeutic agent for scleroderma.