The hepatic effects of repeated anesthesia of phenobarbital-induced Fischer 344 rats with 1% halothane/14% oxygen were investigated, after anesthetics were administered at either 1-day or 5-day intervals. Urinary excretion of fluoride, a product of reductive halothane metabolism, was increased in the 24-h period following anesthesia, but was the same after the first, second, and third anesthetics. Rats killed 24 h after a single anesthetic all had centrilobular hepatocellular necrosis. All animals killed 24 h after the second or third anesthetic also had centrilobular necrosis, but, in most animals, this was no more extensive than that following a single anesthetic, regardless of whether the interval between anesthetics was one or five days.