We investigated the involvement of adenosine in ischemic preconditioning (IPC) by the unspecific antagonist, 8-phenyltheophylline (8-PT). Anesthetized Wistar rats were treated as follows: 1. non-ischemic controls, 2. ischemic controls: 60 min of clamping of the common hepatic artery followed by 60 min reperfusion, 3. IPC: 10 min ischemia followed by 15 min reperfusion, prior to the identical ischemia-reperfusion (IR) period as in group 2, 4. 8-PT + IPC: 8-PT 10 mg/kg i.v. was given 10 min prior to the identical procedure as in group 3. The peripheral liver blood flow was monitored by laser-Doppler flowmetry. Blood alanine aminotransferase (ALT) was analyzed once every 60 min. IPC significantly reduced impairment of liver blood flow, as well as ALT increase during reperfusion. This effect was abolished by pretreatment with 8-PT. Adenosine appears to be a crucial effector in IPC. Clinical studies need to be undertaken to explore a possible effect of IPC in liver transplantation.