A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. Bone mineral density is a complex trait that, presumably, is influenced by multiple genes. Interleukin-6 (IL-6) is an attractive candidate gene for osteoporosis susceptibility, because it has effects on bone cells and has been implicated in the pathogenesis of osteoporosis. Furthermore, previous investigators have identified an association between a 3' UTR polymorphism of the IL-6 gene and BMD. In this study, we searched for linkage and association between this IL-6 gene polymorphism and peak BMD in a large population (812 individuals) of healthy premenopausal sibpairs. Although previous investigators identified only 6 IL-6 alleles, we identified 17 alleles by modifying electrophoretic conditions and evaluating a very large population. We found no evidence for either linkage or association between the IL-6 gene locus and BMD of the spine or hip in either Caucasians or African Americans.