MRL mice, which develop a lymphoproliferative disease characterized by increased numbers of α/β T cell receptor+ (TCR+ ) B220/6B2 + CD4-CD8- T cells [lymphoproliferation (Ipr) T cells], were studied for the effect of the Ipr/lpr mutation on the mucosal immune system in the gastrointestinal (Gl) tract. We analyzed the effect of the Ipr gene mutation on T and B cell populations in the Peyer's patches (PP) and the lamina propria lymphocytes (LPLs), as examples of major IgA inductive and effector tissues in the Gl tract respectively. Normal mouse PP contain B cells committed to IgA (surface lgA+) but only low numbers of B cells producing IgA. However, enhanced spontaneous IgA and IgG synthesis occurs in the PP of MRL mice. Further, we have now shown that PP of MRL mice are populated by Ipr T cells. Interestingly, Ipr T cells were not present in significant numbers in LPLs of MRL mice, even in older animals. Of interest was the finding that the ratio of CD4+ to CD8+ T cells in the lamina propria was lower in MRL when compared with control mice, and the CD8+ T cell subset actually predominates in LPLs of autoimmune mice. In addition, the number of γ/δ TCR+ T cells in LPL of MRL Ipr/lpr mice was significantly increased, especially in MRL Ipr/lpr mice at 6 and 12 weeks of age. When the isotype distribution of B cells in LPLs was analyzed, no changes were noted in MRL Ipr/lpr mice in comparison with MRL +/+ or normal control mice, and the pattern was lgA> >lgM >lgG. These results show that although increased numbers of CD8+ T cells and γ/δ TCR + cells occur in the LPLs of MRL mice, a normal distribution of plasma cell isotypes (lgA> >lgM lgG) is found in this mucosal compartment. Further, Ipr T cells do not develop in the lamina propria compartment of the Gl tract. © 1992 Oxford University Press.