Transfer of CD45RBhigh CD4+ T cells from normal mice to congenic SCID mice induces wasting disease, a murine model of inflammatory bowel disease. In this model, colonic inflammation is considered to be caused by a disregulated Th1 response, and Th1 cytokines, especially IFN-gamma, have been suggested to play an important role in the pathogenesis of wasting disease. In order to elucidate the potential role of IFN-gamma in the pathogenesis of wasting disease, we transferred CD45RBhigh CD4+ T cells from IFN-gamma knockout (GKO) mice to congenic SCID mice. The recipient mice were absolutely free of symptoms and clinical signs of disease and showed body-weight gain similar to that seen in normal mice. These data demonstrate the essential and non-redundant role of IFN-gamma in the pathogenesis of wasting disease.