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 less than 0.016) and class II (HLA-DR, DP) antigens (P less than 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.