There are few studies of the effect of smoking on bone density in young women. The reported antiestrogenic effect of smoking could be a mechanism for a possible effect of smoking on bone. We measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (whole body, proximal femur, lumbar spine), and serum levels (midfollicular phase) of testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), and cortisol in 52 women (25 smokers, 27 nonsmokers) aged 20-35 years. The two groups did not differ significantly in age, height, weight, or the sum of eight skinfold thicknesses. The mean number of cigarettes smoked per day and the number of years of smoking were 16.9 and 12.9, respectively. There were no significant differences in BMD between smokers and nonsmokers at any site. For both smokers and nonsmokers, SHBG and the free androgen index (T/SHBG) made significant contributions (P<0.005) to the variance in BMD at all sitesexcept the lumbar spine. The free estradiol index (E2/SHBG) contributed to whole body BMD (P<0.05). For all subjects, there were significant inverse relationships between SHBG and BMD (P<0.002), and positive relationships between T/SHBG and BMD (P<0.02) for all sites except the lumbar spine. These data suggest that moderate smoking in young women is not associated with low BMD at any site. However, smokers had lower free estradiol and higher SHBG, both of which have been related to increased bone loss in older women.