We previously identified the endogenous DAMP HMGB and the PRR TLR4 to be major mediators of organ damage in hepatic ischemia/reperfusion (I/R).8 Recently, DNA and TLR9 have also been shown to play critical roles.9 Although studies by our group and by others have investigated the function of circulating HMGB1 and DNA in I/R injury, the involvement of histone proteins, which are closely associated with both HMGB1 and DNA in the nucleus, has not yet been examined. This evidence concerns the gene HMGB1 and ischemia.