For many inherited and acquired hepatic diseases, liver transplantation is the only possible therapeutic strategy. Ischemia/reperfusion (I/R) damage to donor tissue is thought to be one component that may play a role in the decline of posttransplant tissue function and ultimately rejection. The transcription factors, AP‐1 and nuclear factor κB (NF‐κB), play important roles in the acute cellular responses to tissue damage, as well as the inflammatory phase following I/R. We have found that the DNA binding activity of AP‐1 was dramatically increased following warm ischemia at 1 to 3 hours postreperfusion. Induced DNA binding activity was composed of predominately c‐Jun and JunD hetero‐ and homodimers as determined by electrophoretic mobility supershift assays. This increase in AP‐1 activity occurred in the absence of significant changes in the steady‐state protein levels of c‐Jun and JunB. Maximal activation of Jun amino‐terminal kinase (JNK) occurred within the 25 to 30 minutes postreperfusion, just before the peak in AP‐1 DNA binding. These findings suggest that phosphorylation may play an important role in regulating AP‐1 transcriptional complexes. Furthermore, JunD protein levels slightly increased at 3 hours postreperfusion, concordant with changes in AP‐1 DNA binding activity. The activation of NF‐κB at 1 hour postreperfusion was independent of proteolytic degradation of IκB‐α or IκB‐β. This activation of NF‐κB DNA binding activity in the nucleus was preceded by an increase in tyrosine phosphorylation of IκB‐α. These studies suggest that JNK, IκB tyrosine kinase, and JunD are potential targets for therapeutic intervention during liver I/R injury.