Rabbit immunization with duodenal or colonic high molecular weight components allowed us to distinguish three new M3 antigens associated with intestinal goblet cells; these were denoted as M3SI, M3D, and M3C. Using immunoperoxidase staining, the anti-M3SI serum labeled all goblet cells in the small intestine, and a certain number of them in the colon, mainly in its proximal part. The anti-M3D serum reacted primarily with the goblet cells of the duodenal villosities, and the anti-M3C serum with all goblet cells of the large, but not the small, intestine. Moreover, the M3C antigen was recovered in some goblet cells of the fetal duodenum, in association with the two other markers. Only the M3D and the M3SI antigens were observed in the normal duodenum and intestinal metaplasia (IM) of benign gastric mucosa. In contrast, IM adjacent to gastric carcinomas, whatever their histological type, contained the M3C antigen in addition to M3D and M3SI antigens, and thus showed an antigenic pattern similar to fetal duodenum. Some gastric carcinomas, especially those with intestinal-like differentiation, produced the colonic M3C antigen as the neighboring IM. Thus, these two tissues displayed common differentiation features, which could be related to fetal duodenum rather than to adult colon.