Expression of class II molecules on intestinal epithelial cells in humans. Differences between normal and inflammatory bowel disease. Expression of class II antigens on human intestinal epithelial cells was assessed using a sensitive avidinbiotin-peroxidase technique. HLA-DR was present predominantly in the normal small bowel with diminished but evident expression in the colon. HLA-DP staining was less prominent, and HLA-DQ was absent. In inflammatory bowel disease the expression of both HLA-DR and HLA-DP was increased, but that for HLA-DQ remained absent, suggesting an inherent defect in the ability of intestinal epithelial cells to express HLA-DQ. In related experiments, an interferon gamma-treated malignant epithelial cell line T84 also failed to stain for HLA-DQ and HLA-DP despite the presence of HLA-DR. Isolated RNAs for all three subclasses of HLA-D were detectable by slot-blot analysis, suggesting that the lack of HLA-DQ expression relates to posttranscriptional defects in intestinal epithelium. These and other differences with conventional class II antigen-positive accessory cells (macrophages/B cells) may help to explain the unique properties of intestinal epithelial cells as antigen-presenting cells. 