Four groups of isolated rat livers underwent perfusion at 37 degrees C for 1 h, at 37, 40, 43 or 45 degrees C, respectively, during the 2nd hour and then at 37 degrees C again for the 3rd hour. Vascular resistance slightly decreased during hyperthermia and then significantly increased after restarting normothermic perfusion. At 40 degrees C bile production, oxygen consumption, glucose and lactate release did not significantly differ from those found in the 37 degrees C group. At 43 and 45 degrees C all these parameters were significantly impaired when compared to the 37 and 40 degrees C groups and did not recover after normothermic perfusion was restored. GOT and GPT release increased in proportion to the temperature. Microscopic examination revealed normal histologic features in 37 and 40 degrees C specimens while alterations such as vacuolization and focal necrosis were found in the 43 and 45 degrees C groups. These data indicate that the highest temperature that is well tolerated by isolated rat livers for 1 h is located between 40 and 43 degrees C.