This study evaluated the additive effects of hormone replacement therapy (HRT) and a 1-year site-specific resistance-training (RT) program involving two free weight exercises (i.e., squat and deadlift) 2 days/week as a strategy to reverse or attenuate bone loss at the lumbar spine in early postmenopausal women. Participants from a group of self-selected HRT or non-HRT (N=141) users were randomly assigned to RT (exercise) or no training, creating four groups: 1) non-HRT plus RT [NHRT plus exercise (n=35)]; 2) HRT plus RT [HRT plus exercise (n=37)]; 3) HRT no resistance training [HRT no exercise (n=35)]; or 4) control [non-HRT no resistance training group (n=34)]. Mean age and months past menopause did not differ between groups (52.1+/-3.0 years and 52.8+/-9.9 months, respectively). Post-menopausal status was confirmed by follicle-stimulating hormone levels > or =40 mIU/mL. Bone mineral density (BMD) of the spine was assessed by Dual Energy X-ray Absorptiometry (Hologic), at baseline and month 12. Data were analyzed using a 4 (experimental condition) x 2 (time) repeated measures multivariate analysis of variance to determine the effects of RT on HRT and non-HRT in early postmenopausal women. The main effects for group (P<0.007), time (P<0.001), and the group by time interaction (P<0.001) were each significant. Control participants experienced an average of -3.6% reduction of BMD at the spine. HRT treatment with no exercise showed bone loss of -0.66%. One year of RT produced increases in spine BMD of +0.43% and +0.70%, respectively for the NHRT plus exercise, and HRT plus exercise groups with no differences between the NHRT and HRT exercise groups. In conclusion, RT alone was as effective as HRT in preventing bone loss at the spine and was more effective than HRT alone in attenuating bone loss at the spine. Moreover, there was no additional benefit in combining HRT with RT for preventing bone loss at the spine in this group of early postmenopausal women.