In a randomized, double blind, clinical prospective trial comprising 35 women treated with either hormone replacement therapy (HRT) (cyclic estradiol/norethisterone acetate) or placebo we performed histomorphometric studies on paired bone biopsies obtained before and after 2 years of treatment. Untreated women developed a progressively more negative balance at individual bone multicellular units (BMUs) (i.e., wall thickness-erosion depth) (2.2 ± 1.7 μm vs. −5.7 ± 1.4 μm; p < 0.01), while women on HRT displayed preservation of bone balance (2.4 ± 2.4 μm vs. 2.5 ± 2.5 μm; NS). No significant differences in wall thickness between the two groups were demonstrable, but the untreated women developed a pronounced increase in erosion depth over 2 years (46.9 ± 1.8 μm vs. 52.0 ± 1.9 μm; p < 0.05), while the HRT group revealed no change (47.8 ± 2.7 μm vs. 44.6 ± 1.7 μm; NS). Furthermore, the placebo group displayed an increased osteoclastic erosion depth (17.8 ± 1.6 μm vs. 25.0 ± 1.7 μm; p < 0.001), compared with unchanged values in the HRT group (20.0 ± 1.6 μm vs. 16.9 ± 1.4 μm/day; NS). While the placebo group revealed a slight increase in volume referent resorption rate (35 ± 8% vs. 38 ± 8%; NS) the HRT group revealed a pronounced decrease (46 ± 8% vs. 28 ± 5%; p < 0.05). No significant changes in marrow star volume (an index of trabecular perforations) were demonstrable in either group. Our results demonstrate that bone remodeling in early postmenopausal women is characterized by progressive osteoclastic hyperactivity, which is reduced by cyclic HRT. This reduction of resorptive activity at the BMU level after HRT seems to precede the reduction in activation frequency demonstrated in previous studies on older postmenopausal women.