The effect of interferon-gamma (IFN-γ) and TGF-β2 on expression of MHC antigens by the human intestinal epithelial cell line HT-29 was examined by immunohistochemistry and flow cytometry. Untreated HT-29 cells constitutively expressed HLA-ABC but little HLA-DR. Expression of both molecules was increased by IFN-γ(100 U/ml, 24 h). TGF-β2 at concentrations × 0·5 ng/ml given before or simultaneously with IFN-γ, inhibited the IFN-induced expression of HLA-DR. Small increases in HLA-ABC expression by IFN-γ were further increased by pretreatment with TGF-β2, while a strong induction of HLA-ABC was inhibited by the TGF-β2 pretreatment. Our results suggest that the inhibitory action of the TGF-β2 on both HLA-ABC and HLA-DR correlates with the degree of induction following IFN-γ treatment. Since TGY-β2 is present in milk and is produced by gut epithelial cells, one of its possible functions may be to regulate expression of HLA antigens in the neonatal intestine and/or diseased intestine.