Previous studies have shown that malignant transformation is sometimes associated with the aberrant expression of HLA class II antigens. The functional significance of such aberrant expression is not known. Since HLA-DR antigen is expressed in normal colonic mucosa, it would be interesting to see if malignant transformation could result in the aberrant suppression of this antigen. Sixteen colonic adenocarcinomas, 29 colonic adenomatous polyps and 23 samples of normal colonic mucosa, including 9 cases of colonic mucosa adjacent to carcinoma, were stained immunohistochemically for HLA-DR antigen. The intensity and distribution of the antigen staining in the cytoplasm and luminal surface of the epithelial elements were analysed semiquantitatively. The lymphoplasmacytic infiltrate in the lamina propria was also evaluated. Cytoplasmic HLA-DR antigen expresion was found to be significantly diminished in moderately and poorly differentiated adenocarcinomas but not in adenomas or well-differentiated adenocarcinomas. This suggests that the change in HLA-DR expression is not intrinsic to the neoplastic process but may merely be due to the fact that malignant cells, as they become less differentiated, tend to show alterations in their antigenic phenotype.