Graft-versus-host reaction (GVHR) is a complex process initiated upon allorecognition. For detection of early molecular events in GVHR, we first assessed time courses with respect to symptoms and serum interferon (IFN)-gamma levels and then used the differential display method to compare gene transcript patterns during the early phase between acute lethal GVHR mice and syngeneic controls. In the GVHR mice, high expression levels of seven genes encoding the following molecules were detected: TGTP/Mg21 (an IFN-gamma -related signaling molecule), vitronectin, Nedd5 (a mammalian septin), manganese superoxide dismutase, activin betaC subunit, PRCC (a papillary renal cell carcinoma-associated molecule), and an uncharacterized gene corresponding to a mouse expressed sequence tag (EST). The expression levels of most genes peaked before the symptomatological onset and the peak of IFN-gamma levels. Thus, gene expression monitoring may characterize the inductive process of GVHR and aid in the development of gene-based diagnostics and therapies.