We have studied the histological changes observed in the mucosa of 10 rats in the region of a esophagojejunostomy to evaluate it as a model for the ulcer-associated cell lineage (UACL). In man, the UACL has a distinctive morphology, proliferative organization, and pattern of trefoil peptide localization. We have therefore examined these aspects aided by immunohistochemistry and in situ hybridization to the trefoil peptides TFF1, TFF2, and TFF3. Only TFF2 was studied by immunohistochemistry, whereas the mRNAs for all three peptides were examined by in situ hybridization using 35S-labeled riboprobes. The marker MIB-1 to the Ki67 proliferation-related antigen was used to examine the proliferative organization of UACL-like changes. In all cases, columnar epithelialization of the distal esophagus was seen, and in all, glands with morphological and gene expression attributes of the UACL were identified. TFF3 mRNA localized patchily throughout the UACL, whereas TFF1 mRNA was found in the upper portions of the lineage and TFF2 mRNA and its product in the acini. These lineages showed virtually no intrinsic proliferative activity. These appearances are similar to those seen in early human UACL, and we therefore propose this that this represents the first published animal model of this lineage.