Interleukin-6 (IL6) has many roles essential to the regulation of the immune response, hematopoiesis, and bone resorption. Three single-nucleotide polymorphisms (SNP) in the IL6 promoter region were genotyped by the single-base extension method. The frequencies of each SNP were 0.002 ( IL6-597 G--> A), 0.27 ( IL6-572 G--> C), and 0.002 ( IL6-174 G--> C) in a Korean population ( n=1,082). IL6-597 G--> A and IL6-174 G--> C were totally linked together ( d(2)=1) and showed very low allele frequencies (0.002), which are common in Caucasians. On the other hand, the frequency of the IL6-572 G--> C*C allele was much higher (0.27) than that in Caucasian populations (<0.07). One of the IL6 promoter SNPs, viz., IL6-572 G--> C, showed significant associations with bone mineral density (BMD), i.e., the C allele was associated with increased BMD ( P=0.02, co-dominant model; P=0.007, dominant model). The mean BMD was highest in homozygous C individuals (0.67+/-0.15), lowest in homozygous G individuals (0.58+/-0.19), and intermediate in heterozygotes (0.64+/-0.21). In the present study, we describe a variant in the IL6 promoter region that shows positive association with higher BMD in a gene-dose-dependent manner in pre-menopausal women.