Seventy post-menopausal women with osteoporosis were randomized into two groups: 40 patients received calcitriol (0.5 microg/day) and calcium (1000 mg/day); and 30 control patients received calcium (1000 mg/day) alone. Thirty healthy women formed the healthy control group. Bone mineral density (BMD) and serum interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured at baseline and after 6 months of treatment. Calcitriol treatment for 6 months significantly increased BMD and reduced serum IL-1 and TNF-alpha concentrations compared with no significant changes in patients treated with calcium alone. Both treatments increased serum calcium and decreased parathyroid hormone concentrations. The healthy control group had a significantly lower IL-6 concentration than the post-menopausal women with osteoporosis. We have shown that calcitriol was an effective treatment for osteoporosis. Significant reductions in serum IL-1 and TNF-alpha concentrations suggest that, in addition to increasing the absorption of calcium, calcitriol may directly affect bone metabolism via cytokines.