Class I and class II (HLA-DR, DP and DQ) MHC antigen expression and the phenotypic nature of the inflammatory infiltrate in gastric and duodenal biopsies in bone marrow transplantation patients with and without graft-versus-host disease were investigated. Increased expression of class I (P<0.016) and class II (HLA-DR,DP) antigens (P<0.002) was associated with GVHD. The epithelium in two GVHD-positive biopsies was HLA-DP-positive and HLA-DR-negative. None of the tissues expressed HLA-DQ. Association between MHC antigen expression and phenotype of infiltrating cell was then examined. The majority of GVHD biopsies showed an infiltrate composed of CD4+cells and CD8+cells. However, the two DP+, DR−biopsies were associated exclusively with CD8+intraepithelial cells, suggesting sequential events in GVHD, with CD8+cells infiltrating tissue first associated with HLA-DP expressions, followed by accumulation of CD4+as well as CD8+cells in association with expression of HLA-DR.