A panel of monoclonal antibodies (MAbs) has been obtained, directed against determinants of normal human colorectal epithelium. BALB/c mice were immunized and boosted with mucosal scrapings and cell membrane preparations from normal large intestine. In one case boosting was also performed with HT29 colon carcinoma cells. Hybridoma supernatants were screened immunohistochemically on frozen sections of normal colorectal epithelium, leading to the selection of 12 MAbs which recognized determinants of the major epithelial cell lineages. These antibodies fall into two groups: group 1 antibodies react with mucus constituents, with or without other cell components; group 2 antibodies react only with non-mucus components of cells. The normal tissue distribution of the antibody panel has been characterized immunohistochemically. Three of the mucus-reactive group-1 antibodies, PR.4D4, PR.5D5 and PR.3A5, and also PR.1A3 of group 2, have a very restricted distribution. In all 4 cases, their reactivity outside the gastrointestinal tract is mainly confined to tracheal epithelium. A series of benign and malignant colorectal tumours has been studied with the antibody panel. The antibodies of group 1, and PR.1A3 from group 2, show a marked heterogeneity in their reactions with malignant cells and seem to be defining patterns of functional differentiation, independently of standard histological criteria. The reactivity of 6 colorectal carcinoma cell lines has also been assessed with the antibodies. The group-1 antibodies and PR.1A3 identify those cell lines which have retained some capacity for differentiation.