The relations of vasomotor symptoms to the rate of bone loss and to the response of forearm bone mineral density (BMD) to hormone replacement therapy (HRT) were analyzed in a 2-year non-randomized study. Forty peri/postmenopausal women who were given HRT for climacteric symptoms were compared with untreated control women, individually matched for age and length of time since the last menstrual period. The women who received HRT gained, on average, about 2% in BMD, while the control women lost about 6% (mean group difference 8%; 95% confidence interval (CI) 5.7-10.2). Adjustment for potential confounders did not change the results. Sweating frequency was inversely correlated with serum estradiol levels (p=0.05). Among untreated women the rate of bone loss was higher in those who had frequent sweating initially than in those with less frequent sweating (9% vs. 4%, mean difference 4.3%; 95% CI 0.7-7.8, p=0.023). Among women who received HRT, those who had the highest frequency of sweating initially, compared with those with a lower frequency, showed a greater gain in bone density (mean difference 4%; 95% CI 1.2-6.8, p=0.007). In multivariate analysis adjusting for covariates, sweating frequency remained an independent determinant of change in bone density in women both with and without HRT. When sweating frequency and serum estradiol levels were compared in a multivariate analysis, only sweating frequency showed an independent association with rate of bone loss. The findings indicate that women with severe climacteric symptoms may have an excessive rate of bone loss and should therefore be considered as a special target group for prevention of osteoporosis. This group of women may be those who will have substantial benefit from HRT both immediately, through relief of climacteric symptoms, and in the long-term with regard to bone loss and fracture risk.