Ischemic preconditioning (IP) protects the rat liver. In pigs, in which hepatic tolerance to ischemia is similar to that in humans, information on IP is lacking. Therefore, in enflurane-anesthetized pigs, hepatic vessels were occluded for 120 min (protocol 1) or 200 min (protocol 2) without (control) and with IP (3 times 10 min ischemia-reperfusion each). In protocol 1, cumulative bile flow (CBF) during reperfusion was greater in IP (47.3 ± 5.2 ml/8 h) than in control (17.1 ± 7.8 ml/8 h, P < 0.05). ATP content tended to recover toward normal during reperfusion in IP, whereas it remained at ischemic levels in control. Serum enzyme concentrations increased similarly during reperfusion, and <1% hepatocytes were necrotic or stained terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive in control and IP groups. In protocol 2, no differences in CBF, ATP, or serum enzyme concentrations during reperfusion were measured between control and IP groups, except for a somewhat reduced lactate dehydrogenase in IP. The number of necrotic or terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes tended to be greater in the IP than the control group. Thus IP provides some functional protection against reversible ischemia but no protection during prolonged ischemia in pigs.