We studied the effects of ATP and epinephrine on distribution of ischemic hepatic tissue flow in the isolated perfused rat liver. Five minutes after clamping both the portal vein and hepatic artery, perfusion was started. Lidocaine was infused into the portal vein, and the concentration of lidocaine in hepatic outflow was measured with FPIA. The oxygen extraction ratio was also measured. Tissue surface blood flow was measured with laser-Doppler flowmetry. We measured the tissue flow at 2 points: one where flow was more than 10 ml.min-1.100 gm liver weight-1 (R), and the other where flow was less than 10 ml.min-1.100 gm liver weight-1 (P). After perfusion pressure had become stable, ATP or epinephrine was infused for 15 minutes. Perfusion pressure increased, and tissue flow of R decreased significantly, while that of P increased (not significantly). The extraction ratio of lidocaine decreased significantly by epinephrine, and that of oxygen decreased (not significantly). We conclude that in the ischemic liver, vasoconstriction results in changes in the distribution of tissue blood flow and alters drug metabolism.