High levels of insulin-like growth factor (IGF)-I are reported to be associated with an increased risk ofprostate cancer. On the other hand, the insulin-like growth factor binding protein-3 (IGFBP-3) may decreasethe risk. We therefore investigated the influence of serum IGF-I and IGFBP-3 on prostate cancer risk in a casecontrolstudy nested within a large-scale cohort in Japan (the Japan Collaborative Cohort Study). Informationon lifestyles and sera of the subjects were collected in 1988-90. Serum IGF-I, IGF-II and IGFBP-3 were measuredin sera stored at -80°C by immuno-radiometric assay. In 13,508 male subjects of the cohort who donated sera,40 cases and 120 controls (1:3 matched with age and survey area) were identified. Ages of the cases ranged from59 to 79 years, with a mean of 69.8. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated forthe highest and middle tertiles compared with the lowest in controls using a conditional logistic model. NonadjustedORs for the highest tertiles were 0.99 (95% CI, 0.34-2.91) for IGF-I (trend-P = 0.60), 1.91 (95% CI,0.68-5.38) for IGFBP-3 (trend-P = 0.23), 1.73 (95% CI, 0.69–3.47) for IGF-II (trend-P = 0.23), and 0.67 (95% CI,0.26-1.76) for the IGF-I/IGBP-3 ratio (trend-P = 0.83). Serum levels of IGF-I, IGF-II, IGFBP-3, or IGF-I/IGFBP-3 ratio were thus not thought to be associated with risk of prostate cancer.