Space flight and bedrest result in a negative calcium balance and osteopenia. The mechanisms underlying these events are not well understood. In particular, it is not clear whether systemic or local factors are preeminent in mediating the effects of gravity on bone mineral content. Using a rat model that unweights only the hindlimbs, we determined whether the osteopenia induced in these rats was generalized or restricted to the unweighted limbs, and whether changes in intestinal calcium transport contributed to the alterations in bone calcium content. In this model, the hindquarters were elevated using the tail at an approximately 40 degrees angle for up to 15 days. The tibia and lumbar vertebra from experimental rats contained substantially less calcium than the same bones from pair-fed controls; at 15 days, the tibia was 86.2 +/- 2.5% of the control value (mean +/- SE), and the vertebra was 75.5 +/- 3.5% of control value (mean +/- SE). However, these differences were found only for the unweighted bones; the mandible and humerus showed no differences between experimental and pair-fed control rats. When calcium uptake by bone was evaluated after 45Ca administration, we observed an initial decrease in uptake at 5 days only in the tibia [percentage of control value, 60.5 +/- 5.5, (mean +/- SE)] and vertebra (percentage of control value, 74.3 +/- 3.7) when experimental animals were compared to pair-fed controls; there was no decrease in the humerus and mandible. However, after 10 days of unweighting , calcium uptake in the tibia and vertebra of experimental animals returned to control levels and by 15 days exceeded control levels (the tibia was 125.8 +/- 5.8% of the control value and the vertebra was 136.2 +/- 9.6% of the control value) despite the progressive decrease in total bone calcium compared to that in pair-fed controls. At no time could we demonstrate a difference in duodenal calcium transport between experimental and control animals. These data suggest that in this model, which simulates certain aspects of weightlessness, changes in local factors within the unweighted bones may have a greater impact on bone mass and turnover than changes in systemic factors that regulate overall bone mineral homeostasis.