While the urban-rural difference in bone mineral density (BMD) has been shown in some, but not all, Western populations, such a difference and the reason for the difference is largely unknown, particularly in developing countries. This cross-sectional, epidemiologic study was designed to examine the hypothesis that differences in measures of body composition such as lean mass (LM) and fat mass (FM) contribute to the urban-rural difference in BMD. Lean mass, fat mass, lumbar spine and femoral neck BMD were measured by DXA (GE Lunar Corp, Wis.) in 411 urban (Bangkok city) and 436 rural (Khon Kaen province) Thai subjects, aged 20-84 years. Rural men and women had significantly higher LM and lower FM than their urban counterparts. In multiple linear regression analysis, age, LM, menopausal status (in women) and residence were independent determinants of BMD. After adjusting for age, menopause and LM, rural subjects were found to have significantly higher femoral neck BMD, but not lumbar spine BMD, than urban subjects. Furthermore, to alleviate the potential effect of multicolinearity of LM and FM, each rural subject was matched with each urban subject for FM and age, which resulted in 46 pairs of men and 91 pairs of women. In this matched-pair analysis, the femoral necks in rural men and women were, respectively, 7.3+/-2.1% (mean+/-SE; P<0.01) and 6.3+/-2.8% (P<0.02) higher than in urban men and women. The urban-rural difference in LM accounted for approximately 23 and 5% of the urban-rural difference in femoral neck BMD in men and women, respectively. These data are thus consistent with the hypothesis that the urban-rural difference in BMD at a weight-bearing site is in part associated with the urban-rural difference in lean mass.