Increased expression of the type I insulin-like growth factor receptor (IGF-IR) is associated with colon cancer, while the antioxidant N-acetyl-L-cysteine (NAC) is known to suppress colonic proliferation. We demonstrate that NAC down-regulates the expression of IGF-IR on three colorectal adenocarcinoma cell lines (HT29, SW480, and LoVo). NAC also abrogates the proliferative effect of IGF-I on HT29 cells. This indicates a novel mechanism for the therapeutic effects of NAC.Increased expression of the type I insulin-like growth factor receptor (IGF-IR) is associated with colon cancer, while the antioxidant N-acetyl-L-cysteine (NAC) is known to suppress colonic proliferation. We demonstrate that NAC down-regulates the expression of IGF-IR on three colorectal adenocarcinoma cell lines (HT29, SW480, and LoVo). NAC also abrogates the proliferative effect of IGF-I on HT29 cells. This indicates a novel mechanism for the therapeutic effects of NAC.