Municipal water fluoridation has notably reduced the incidence of dental caries and is widely considered a public health success. However, ingested fluoride is sequestered into bone, as well as teeth, and data on the long-term effect of exposure to these very low doses of fluoride remain inconclusive. Epidemiological studies suggest that effects of fluoride on bone are minimal. We hypothesized that the direct measurement of bone tissue from individuals residing in municipalities with and without fluoridated water would reveal a relationship between fluoride content and structural or mechanical properties of bone. However, consonant with the epidemiological data, only a weak relationship among fluoride exposure, accumulated fluoride, and the physical characteristics of bone was observed. Analysis of our data suggests that the variability in heterogenous urban populations may be too high for the effects, if any, of low-level fluoride administration on skeletal tissue to be discerned.