In the gut, both the villus epithelium and cells of macrophages and dendritic cell lineages of the lamina propria and Peyer's patches express major histocompatibility complex (MHC) class II glycoproteins and have the potential to present soluble protein antigen. Using mice transgenic for the X and Y promoter deletion mutants of the gene encoding the I-Ek alpha class II protein we have shown: that an intact promoter is essential for expression of I-Ek alpha on the epithelium and lamina propria macrophages; that only the Y box is essential for expression by lamina propria dendritic cells; and that dendritic cells in Peyer's patches are phenotypically more restricted than in the lamina propria and express I-Ek alpha under different regulatory control mechanisms. The results show that different inductive mechanisms exist for class II in distinct mucosal cell populations and provide a model for the analysis of differential antigen handling in the gut mucosa.