Forty-eight human colorectal adenocarcinomas, removed at different stages of development, have been examined immunohistochemically for the expression of class II molecules and for the relationship of such class II expression to infiltrating leukocytes. Forty-four% of tumor epithelium samples express class II molecules. This expression is confined to the proteins coded for by the HLA-D/DR subregion although the surrounding infiltrating cells express HLA-D/DR, -DQ, and -DP coded proteins. In addition, there are significantly greater numbers of mononuclear phagocytes and T-cells of the CD8 antibody-positive subset associated with the tumors expressing class II molecules on tumor epithelium compared to the class II-negative tumors. The T-cells appear not to be activated judging by the lack of expression of the receptor for interleukin-2 but the mononuclear phagocytes express CR1, the receptor for the complement component C3b, which suggests that they are stimulated.