The purpose of this study was to investigate the effects of 10 years of hormone replacement therapy (HRT) in postmenopausal women on bone mineral density of the lumbar spine (L-BMD) and bone mineral content of the distal forearm (F-BMC). A total of 151 women were enrolled in the study, 100 of whom were randomized to receive oral HRT (equally divided between a continuous combined and a sequential treatment regimen), with the remaining 51 receiving placebo or no treatment. The study was double-blind for the first 24 months, followed by 8 years of open-label follow-up, Total treatment duration was 10 years, At the end of 10 years, 38% of women randomized to continuous combined HRT remained on therapy compared with 22% of those who had received sequential HRT and 49% of the untreated group, A further 18% of women originally randomized to HRT had switched to other regimens, After 10 years of therapy, L-BMD was found to be significantly higher in HRT-treated women than in those who remained untreated (14.5%; p < 0.001), corresponding to an increase in L-BMD of 13.1% from baseline values on HRT compared with a reduction in L-BMD of 4.7% without therapy, L-BMD increased by 15.9% in women receiving continuous combined therapy compared with 11.1% in those on sequential HRT; however, intergroup differences were not statistically significant, F-BMC decreased by 0.7% over the 10 year period in the HRT treatment groups compared with a reduction of 17.6% in untreated women (p < 0.001), Mean F-BMC was 20.3% higher in women who had received HRT than in those who had not received therapy at the end of the 10 year follow-up, In conclusion, 10 years of treatment with HRT resulted in a substantial increase in L-BMD, with F-BMC also significantly higher in the HRT group than in untreated women, These results confirm that long-term HRT exerts a continuous effect against bone loss in postmenopausal women. (C) 1996 by Elsevier Science Inc.