Strains induced in the skeleton by functional activity are critical to the homeostasis of bone tissue. An in vivo model of disues osteopenia was used to examine whether the removal of these regulatory stimuli induces a uniform loss of crotical bone through the whole organ or whether the loss of bone is focused at specific sites of the cortex. The right radii of five adult male turkeys were isolated from their normal functional loading for 8 weeks. The corresponding left radius from each animal served as an intact contralateral control. An additional group of five turkeys was used as time-zero controls to assess the initial areal symmetry of the left and right radii. Areal properties were assessed at three sites at equal intervals spanning the middle 3 cm of the diaphysis. Adaptation was determined for each cross section as a whole, as well as specifically by site by division of each cross section into 12 equal angle sectors. The average across all experimental sections after 8 weeks of disuse was 12.1 ± 1.9% (± SE) loss of bone mass. The change in mean cross-sectional area varied little between the three diaphyseal sites (−10.2 ± 3.3%, −13.5 ± 3.8%, and −12.6 ± 4.0%) and occurred primarily (84%) by uniform expansion of the endosteal envelope. However, elevated intracortical porosity following 8 weeks of disuse was highly nonuniform, with 58% of the increased porosity preferentially located in the ventral/caudal cortex (representing only 25% of the cortical area). From these data, it is concluded that bone responds to the removal of functional stimuli with a uniform, organ-wide loss of mass, yet intracortical remodeling occurs preferentially within specific areas of the cortex. The lack of spatial coupling between these events suggests that the two processes may be governed by distinct physiologic criteria.