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Insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the risk of several epithelial or glandular tumors, including prostate cancer, breast cancer, and colon cancer. Cervical cancer, which is also of epithelial origin, has been shown to overexpress receptors for IGF-I, and plasma levels of IGF-I have been positively associated with cervical cancer precursors in one epidemiologic study. In this case-control study, we investigated plasma levels of IGF-I and IGFBP-3 in relation to the risk of histologically confirmed high-grade cervical intraepithelial neoplasia (HGCIN) and the risk of human papillomavirus (HPV) infection. Included in this analysis were 329 cases and 621 controls recruited from clinics affiliated with two Montréal-area hospital centers. We observed a reduced risk of HGCIN for increasing levels of IGF-I, with an adjusted odds ratio (OR) of 0.40 (95% confidence interval, 0.19-0.87) for the highest quartile relative to the lowest quartile of IGF-I. No association was observed between IGFBP-3 levels and HGCIN. Among controls, IGF-I was associated with a decreased risk of being positive for HPV-16 or HPV-18, with an adjusted odds ratio of 0.20 (95% confidence interval, 0.05-0.87) for the highest quartile relative to the lowest quartile of IGF-I. There was no association observed between IGFBP-3 levels and HPV infection status. IGF-I-mediated effects seemed to predominate among women <30 years of age. In contrast to the previously reported study, our results suggest that levels of IGF-I in young women may be inversely associated with HGCIN, a precursor to cervical cancer.