Insulin-like growth factor (IGF)-I has mitogenic and antiapoptotic effects on breast cancer cells. High-circulating IGF-I was found to be associated with increased risk of breast cancer in several previous epidemiological studies, mostly conducted in the Caucasian populations. Little is known about the association between IGF and breast cancer in Asian women whose dietary habits differ considerably from their Caucasian counterparts. A population-based case-control study was conducted to assess the associations of IGFs and IGF binding protein-3, a major IGF binding protein in the circulation, with breast cancer risk in Chinese women. The study included 300 incident breast cancer patients diagnosed between August 1996 and March 1998 in Shanghai and 300 age- and menopause-matched controls selected randomly from the general population. Plasma levels of IGF-I, IGF-II, and IGFBP-3 were measured using commercial ELISA kits (Diagnostic Systems Laboratories, Webster, TX). Conditional logistic regression analysis was performed to examine the association between IGF and breast cancer risk after adjusting for potential confounding factors. Breast cancer patients had higher plasma levels of IGF-I and IGFBP-3. A dose-response relationship was observed between breast cancer risk and the level of IGF-I or IGFBP-3. The adjusted odds ratios were 2.01 (95% confidence interval, 1.26-3.19) or 3.01 (95% confidence interval, 1.81-4.99), respectively, for women with the highest tertile of IGF-I or IGFBP-3 compared with those with the lowest tertile of these molecules. These associations were more evident in premenopausal women or women with high body mass index or high waist-to-hip ratio. No significant association was found for IGF-II. The study confirms that high circulating levels of IGF-I are associated with elevated risk of breast cancer. In contrast to the findings from several studies conducted in Caucasian women, we found that IGFBP-3 was positively associated with breast cancer risk in Chinese women.