The major histocompatibility complex (MHC) status of normal, inflamed, pre-malignant and malignant epithelia of the human gastrointestinal tract was investigated by immunocytochemical methods using monoclonal antibodies (MAbs) directed against heavy (alpha)- and light (beta 2m)-chain Class-I molecules and sub-locus products (DP, DQ, DR) of the HLA-D region. Class-I expression on epithelial cells appeared to vary little with pathological status except in the case of 4/32 (13%) colorectal carcinomas in which the antigens were undetectable or scanty. The pattern of Class-II expression was more complex. The antigens were readily detectable on normal stomach epithelium, in villous adenomas and in inflammatory bowel mucosa. In each of these situations DR was the predominant specificity, followed by DP and DQ. Expression on normal colonic epithelium was usually negative but, in the vicinity of a neoplasm or an area of marked leukocyte infiltration, Class-II molecules (DR greater than DP much greater than DQ) were detectable. A similar pattern of non-coordinate expression was found on 23/32 (72%) colorectal carcinomas, but on the remaining 28% no Class-II products were detectable, under conditions wherein stromal leukocytes were strongly stained. The data suggest that in a significant proportion (nearly 30%) of primary colorectal carcinomas, the capacity for Class-II induction, a constitutive or acquired feature of normal colorectal epithelium, is either diminished or lost. Also, tumor Class-II status is not correlated to Dukes' stage or differentiation.