Studies on the association between vitamin D receptor (VDR) polymorphism and bone mineral density (BMD) in different populations have produced conflicting results probably due to ethnic differences in the populations studied. The Brazilian population is characterized by a very broad genetic background and a high degree of miscegenation. Of an initial group of 164, we studied 127 women from the city of São Paulo, aged 20 to 47 years (median, 31 years), with normal menses, a normal diet and no history of diseases or use of any medication that could alter BMD. VDR genotype was assessed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. BMD was measured using dual energy X-ray absorptiometry (Lunar DPX) at the lumbar site (L2-L4) and femoral neck. Most of the women (77.6%) were considered to be of predominantly European ancestry (20.6% of them reported also native American ancestry), 12.8% were of African-Brazilian ancestry and 9.6% of Asian ancestry, 41.0% (52) were classified as bb, 48.8% (62) as Bb and 10.2% (13) as BB. The BB, Bb and bb groups did not differ in age, height, weight, body mass index or age at menarche. Lumbar spine BMD was significantly higher in the bb group (1.22 +/- 0.16 g/cm2) than in the BB group (1.08 +/- 0.14; P < 0.05), and the Bb group presented an intermediate value (1.17 +/- 0.15). Femoral neck BMD was higher in the bb group (0.99 +/- 0.11 g/cm2) compared to Bb (0.93 +/- 0.12) and BB (0.90 +/- 0.09) (P < 0.05). These data indicate that there is a significant correlation between the VDR BsmI genotype and BMD in healthy Brazilian premenopausal females.