Besides its metabolic role, butyrate, a by-product of colonic fermentation, can modulate colonocyte proliferation and the expression of various molecules. In inflammatory bowel diseases, epithelial cells express HLA class II molecules and may behave as antigen-presenting cells. This study was performed to characterize the effect of butyrate on major histocompatibility complex expression by human colonocytes in comparison with interferon-gamma. Five cell lines displaying different differentiation features were analysed for antigen expression by flow cytofluorimetry. All lines expressed class I antigens, whereas only SW 1116 cells express HLA-DR. On these cells, butyrate and interferon-gamma strongly enhanced HLA-DR and ICAM-1 expression, whereas a mild increase in class I antigens was noted. Moreover, an increase in class I antigens was observed on two other differentiated cell lines, and it was synergistic with interferon-gamma. Butyrate, by its modulation of HLA-DR, ICAM-1 and HLA class I expression, may act on antigen presentation and, thus, influence some inflammatory processes.