Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme abundantly expressed in liver and kidney cells; it is encoded by a single gene that is absent in 20% of the Caucasian population. Our group found that some liver transplantation patients developed de novo immune hepatitis (IH) and that all of them had anti-GSTT1 antibodies. The main objective of this study was to analyze the influence of a GSTT1 mismatch between donor and recipient in the immune response and the outcome of the graft. We confirmed that only under one of the four possible genetic combinations (null recipient/positive donor) is an alloimmune response triggered with production of anti-GSTT1 antibodies. Therefore, we conclude that this genetic mismatch can be considered a risk factor for de novo IH.