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To delineate the influence of mechanical unloading on the osteogenic potential, the effects of mechanical unloading on the trabecular bone formation and the development of osteoblastic cells from bone marrow cells were examined using neurectomized mice. The trabecular osteoclasts and the osteoclastogenic potential of the bone marrow cells were also assessed. In 14 days after sciatic neurectomy, trabecular bone volume in the proximal tibial metaphysis was significantly reduced. The double-labeled surface and bone formation rate (BFR/BS) were significantly reduced. While the numbers of the total bone marrow cells and the nonadherent cells in the neurectomized limbs were not signficantly smaller than that of the sham-operated loaded limbs, the number of the adherent cells in the unloaded limbs was significantly reduced. The number of CFU-f colonies did not differ, but the number of bone nodules developed from bone marrow cells was significantly reduced in the unloaded limbs. The osteoclast-like cell development was increased when the bone marrow cells were incubated with parathyroid hormone. But, the number of CFU-GM colonies did not increase in the unloaded limbs. These data confirmed that the reduction in trabecular bone formation was associated with the reduction in the adherent stromal cells and bone nodule formation of bone marrow cells in the mice tibia after neurectomy. However, in vitro assays including CFU-f and CFU-GM did not identify the changes by unloading. The mechanical unloading affects the development of the bone cells, but may not greatly enhance the capacity for osteoclastogenesis in the bone marrow.