OBJECTIVE: IGF-binding protein (IGFBP)-1 is negatively regulated by insulin. We determined whether the measurement of IGFBP-1 in serum is a useful marker of insulin resistance. RESEARCH DESIGN AND METHODS: Twenty-three subjects underwent a euglycemic insulin clamp. Glucose disposal rates (M) were then correlated with measurements of IGFBP-1, fasting insulin levels, homeostasis model assessment (HOMA), and BMI. RESULTS: IGFBP-1 levels more strongly correlated with M (R = 0.73) than the other parameters such as BMI or HOMA. The level of this protein decreased in individuals who became more insulin sensitive by exercise training. CONCLUSIONS: These studies show a strong correlation between insulin sensitivity and the serum levels of IGFBP-1. These studies suggest, therefore, that measurement of this protein may be valuable in identifying those individuals with insulin resistance and those individuals who respond to interventional strategies.