PURPOSE: To determine whether computed tomography (CT) can be used to quantify age- and site-related changes in cortical bone mineral density (cBMD) at the middiaphyseal femur and whether cBMD differences are related to intracortical porosity. MATERIALS AND METHODS: Cortical bone specimens from 163 femurs were studied with CT and microradiography. Femurs were from 77 males and 86 females in a white anthropologic collection covering a broad age spectrum. In each sample, the cBMD was measured in the entire cortical width and in periosteal, midcortical, and endosteal subregions of interest. Age- and site-related changes in cBMD were tested for significance by using a two-way analysis of variance for both sexes. By using linear regression, cBMD was compared with porosity in the entire cortical width and in each subregion. RESULTS: There were significant age-related differences in cBMD (P < .001 in females, P = .008 in males). In addition, cBMD values were significantly different between the three cortical subregion (P < .001 for both sexes), decreasing from the periosteum to the midcortex to the endosteum. The cBMD values were closely related to porosity, and porosity contributed to 71.6% of the variance in cBMD in the overall population. CONCLUSION: CT is effective in the measurement of age- and site-related changes in cBMD. Decreases in cBMD are closely correlated with increased cortical porosity.