Osteoporosis is a major public health problem, mainly characterized by low bone mineral density (BMD). BMD is a complex trait that is determined by multiple genes. Insulin-like growth factor I (IGF-I) is an important growth factor of bone and thus IGF-I gene has been considered as an attractive candidate gene for osteoporosis. A few studies on the relationship between variants of the IGF-I gene and BMD variation, via traditional association and/or linkage methods, have yielded conflicting results. In this study, we simultaneously tested association and/or linkage of a cytosine-adenine (CA) repeat polymorphism at 1 kb upstream of the transcription initiation site of the IGF-I gene with BMD variation in a large cohort of premenopausal Chinese women. A total of 1263 subjects from 402 Chinese nuclear families were examined. Each family consists of both parents and at least one daughter aged between 20 and 45 years. BMDs (g/cm(2)) at the lumbar spine and hip were measured using dual-energy X-ray absorptiometry (DXA). Applying the QTDT (quantitative transmission disequilibrium tests) progam, we did not find significant evidence of association or linkage between the CA repeat polymorphism of the IGF-I gene and BMD variation at any skeletal site. Our data do not support the IGF-I gene having major effect on BMD variation in premenopausal Chinese women.