AbstractIa antigens were localized in cryostat sections of rat intestine and other tissues by an indirect immunoperoxidase technique using monoclonal antibodies that recognize the rat antigens homologous to the gene products of the I‐A and I‐E subregions of the mouse major histocompatibility complex (MHC). Two categories of Ia+cells were characterized, namely epithelial cells and bone marrow‐derived cells with dendritic morphology. In the small intestine Ia antigen was present in the distal 2/3 of the absorptive epithelium but absent from the bases of the villi, the crypts and the epithelium covering the Peyer's patches. The distribution in nude rats was similar, indicating that T lymphocytes are not obligatory for its expression. In ontogeny Ia antigen was absent in the epithelium of neonatal gut, appearing at about 4 weeks of age and reaching adult levels at about 6 weeks. Different rat strains showed large differences in the amount of Ia antigen expressed by villus epithelium and the traits for the level of expression were shown to map outside the MHC. The levels of expression of Ia antigen in the proximal tubules of the kidney followed that of the gut epithelium in the different strains and in both tissues was mostly intracellular. Studies with chimeras showed that the Ia antigen in epithelial cells was not acquired from bone marrow‐derived cells.The second category of cell studied had a characteristic dendritic morphology and was present in large numbers in the lamina propria of the villi and in the crypts. In the Peyer's patches these cells were present both in the subepithelial dome region and within the epithelium itself. These Ia+dendritic cells were present in nude rat jejunum and appeared in normal fetal gut by 18 days gestation and were also shown to migrate into antigen‐free grafts of fetal gut. This suggests that they do not require stimulation from antigens, bacterial products or T lymphocytes in order to localize in the gut or to express Ia antigen. Studies with other cell surface markers suggest that the Ia+cells with dendritic morphology represent a range of cell types, some with similarities to macrophages and others to nonphagocytic dendri