The zonation of the purinergic action of AMP in the hepatic parenchyma was investigated in the bivascularly perfused rat liver by means of anterograde and retrograde perfusion. Livers from fed rats were used and AMP (100 microM) was infused according to four different experimental protocols: (A) anterograde perfusion and AMP infusion via the portal vein; (B) anterograde perfusion and AMP infusion via the hepatic artery; (C) retrograde perfusion and AMP via the hepatic vein; (D) retrograde perfusion and AMP via the hepatic artery. The response of the liver cells was heterogeneous. Oxygen uptake inhibition by AMP predominates in cells situated shortly after the intrasinusoidal confluence of the portal vein and hepatic artery. Oxygen consumption in all other cells seems to be increased by AMP. Glycogenolysis stimulation by AMP (glucose release) was more pronounced in the periportal cells situated in the region of the intrasinusoidal confluence of the portal vein and the hepatic artery. It can be concluded that the heterogenic response of the liver to AMP is similar to the heterogenic response to ATP.