Thioacetamide-induced hepatoxicity was potentiated in male Sprague-Dawley rats rendered diabetic by alloxan or streptozotocin. The response was more striking in alloxan-diabetic rats. Insulin administration prevented the potentiation following alloxan pretreatment. Fasting also resulted in an enhanced hepatotoxic response to thioacetamide, but the increase was much less than that observed in rats given the diabetogenic agents. The ketosis produced by alloxan was more severe than that induced by streptozotocin, but was unlike that caused by fasting. Pretreatment with phenobarbital, 3-methylcholanthrene or 3,4-benzpyrene did not enhance thioacetamide liver injury.