Insulin-like growth factor (IGF)-I and IGF-II are important mitogen and IGF binding protein-3 (IGFBP-3)exerts opposite effects. However, the results of epidemiological studies on cancer influence are somewhatcontroversial, and mainly from Western countries. In the present study, we therefore examined associations ofserum IGF-I, IGF-II and IGFBP-3 with colorectal cancer risk among participants in the JACC Study in Japan.After matching 3 controls to cases by sex, age, and study area, a total 101 risk sets were examined using aconditional logistic regression model adjusted for body mass index, smoking habit, alcohol consumption andfamily history of colorectal cancer. The odds ratios (and 95% CIs) for colorectal cancer mortality among thehighest tertiles of IGF-I, IGF-II, and IGFBP-3, compared to the lowest tertiles were 1.01 (0.49-2.10), 1.02 (0.55-1.91), and 1.22 (0.63-2.38), respectively. No linear trends were observed. The lack of any association was notaltered after additional adjustment for mutual markers of IGF-I/IGF-II or IGFBP-3, 0.76 (0.34–1.71) for IGFI,0.66 (0.30–1.45) for IGF-II, and 1.11 (0.47-2.66) for IGFBP-3. Our prospective data thus indicated that thereis no association of IGF-I, IGF-II, and IGFBP-3 with colorectal cancer risk in the Japanese population. Althoughthese markers might be etiologically significant in relation to colorectal cancer, we did not obtain evidencesupporting this hypothesis.