Class II antigens in involved colonic epithelia of ulcerative colitis (UC), Crohn's disease (CD), colorectal cancer, and epithelia of normal small intestine were investigated using an immunoperoxidase method. Ten normal colonic mucosa served as normal controls. Ten specimens were studied for each group. Normal colonic epithelia did not express class II antigens. In colonic diseases; (1) with regard to the frequency and extent of class II antigens on epithelia. HLA-DR antigens were the most highly and greatly expressed, followed by HLA-DP and then HLA-DQ antigens. (2) The extent of HLA-DR and -DP, but not HLA-DQ, expression on epithelia of UC and colorectal cancer seemed to be positively correlated with the degree of mononuclear cell infiltration in the lesion. (3) The extent of class II antigen expression on colonic epithelia in CD was not related to the degree of mononuclear cell infiltration in the lesion. (4) The extent of HLA-DR and -DP expression on epithelia of colorectal cancer seemed to be positively correlated with increasing undifferentiation. In the normal small intestine, where HLA-DR antigens were physiologically expressed on epithelia. HLA-DQ antigens were not expressed. The heterogeneity among colonic diseases, and between the physiological and pathological status, may reflect differences in immunoregulation.