To investigate the molecular details of antigen presentation by cells of lymphoid or epithelial origin, we compared B7 mRNA regulation in intestinal epithelium with that in spleen, since both cell types express class II major histocompatibility complex (MHC) and present antigen. As measured by cDNA amplification using sequence-specific primers, IA beta mRNA content was found to be similar in mouse full-thickness small intestine, isolated intestinal epithelial cells and spleen. However, in contrast to IA beta, B7 mRNA intestinal epithelial cell content was markedly lower than in spleen and whole small bowel; cardiac RNA was negative for both sequences. Administration of intraperitoneal interferon-gamma (IFN-gamma)(10 (5) U daily for 2 days) to adult mice resulted in an increase in IA beta mRNA in epithelial cells, but did not alter levels of B7 mRNA. In addition, exposure of the IEC-6 rat cell line to the IFN-gamma resulted in a dose-dependent increase in IA beta mRNA without altering levels of B7 mRNA. Thus, an apparent dichotomy exists in regulation of B7 and IA beta gene expression in rodent intestinal epithelial cells. Since maximal T-cell response to splenocytes depends on B7, the absence of B7 mRNA in intestinal epithelium may be a factor in determining why antigen-presenting enterocytes normally do not elicit damaging T-cell proliferative responses.