The liver is a major target organ of graft-versus-host disease. We have induced graded intensities of acute GVHD to minor histocompatibility antigens in a well-characterized murine bone marrow transplant model and analyzed hepatic pathology one month after BMT. Nuclear-magnetic-resonance relaxation times and proton spectra were compared to systemic clinical disease, serum biochemistries, and histologic findings. T 2 relaxation times correlated directly with the intensity of histologic abnormalities, but the hepatic histology remained mild even in animals with moderate GVHD. In contrast, NMR proton spectra of hepatic tissue showed large decreases in metabolite levels (acetate and glycogen) in animals with moderate systemic disease despite mild hepatic histology. We conclude that NMR of the liver can be used to differentiate hepatic from systemic GVHD in this model and may help to elucidate the differential effects of GVHD in various target organs.