MAM-6 antigen is detectable in a large variety of formalin fixed and paraffin embedded normal and neoplastic tissues throughout the body with some exceptions. One such exception is the large intestine in which normal mucosa has been found negative for MAM-6, while colorectal carcinomas express the antigen in almost all cases. We examined the expression of MAM-6 in 147 benign epithelial tumors (adenomas) of the colorectum and compared this with the detectability of the antigen in 123 colorectal cancers and in 108 non-neoplastic mucosa specimens. The tissue samples were subjected to an indirect immunoperoxidase assay applying the MoAb 115D8 which recognizes the epitope "a" of MAM-6. A majority of the carcinomas (99.2%) and of the adenomas (61.4%) exhibited reactivity for MAM-6 "a", whereas only 8 of the 108 non-neoplastic biopsy specimens (= 7.4%) exhibited faint focal staining. In adenomas, positive reactions were only seen in highly dysplastic tissue areas, in part reflecting carcinomata in situ. The reactivity in four non-neoplastic tissue samples could be explained by shedding of the antigen from carcinomas into glandular structures of the mucosa. Two out of 32 cases exhibiting severe colitis were also focally positive. The detectability of MAM-6 "a" in routinely processed specimens from the large intestine is therefore considered as being closely associated with malignant and premalignant processes. According to a limited study with the antibodies 139H2 and 140C1, this holds true for two additional MAM-6 epitopes. MAM-6 might be considered as a marker of severe (premalignant) dysplasia in adenomas of the large intestine. Further studies are needed to clarify if there is a biological (possibly prognostic) difference between MAM-6 positive and negative high epithelial atypia in these adenomas.