MUC1 mucin has a unique immunogenic peptide epitope in the extracellular domain, which has been shown to induce humoral and cellular immune response. In this study, we evaluated the pathophysiological significance of circulating anti-MUC1 mucin core protein IgG antibodies (anti-MUC1 antibodies) in colorectal cancer by Western blot analysis and 51Cr release assay. Anti-MUC1 antibodies were detected in 5 of 31 (16.1%) healthy subjects and in 27 of 56 (48.2%) patients with colorectal cancer. The presence of circulating anti-MUC1 antibodies was not significantly correlated with the level of circulating antigen MUSE11 or with other clinicopathological parameters tested. The incidence of positivity for anti-MUC1 antibodies in stage I and II (staged according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon and Rectum of the Japanese Research Society for Cancer of the Colon and Rectum) cancers was 45.5% and 58.8%, respectively, suggesting that positivity for these antibodies may be of use as an adjunct for the diagnosis of colorectal cancer in the early stages in the absence of serious complications such as liver diseases. Because of the epitope similarity, anti-MUC1 antibodies in the serum may function in a manner similar to that of anti-MUC1 peptide monoclonal antibodies (mAbs). We therefore observed antibody-dependent cell mediated cytotoxicity with anti-MUC1 peptide mAb using MUC1 cDNA-transfected colon cancer CHC-Y1 cells as the target. The decreased sensitivity of MUC1 transfectants to effector cells was restored to a level equivalent to that in control cells. These data suggest that the detection of circulating anti-MUC1 antibodies may be a useful adjunct for the early diagnosis and immunological analysis of colorectal cancer.