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Eleven adults with refractory leukemia treated with a combination of 6-mercaptopurine and Adriamycin developed hepatic dysfunction manifested by elevations of serum total bilirubin, alkaline phosphatase, and glutamic oxaloacetic transaminase. Liver tissue obtained at necropsy showed intrahepatic cholestasis (eight cases), hepatocellular necrosis (ten cases), leukemic infiltration (two cases), and fatty change (nine cases). Neither this frequency nor severity of hepatocellular destruction has hitherto been associated with 6-mercaptopurine at the dose levels used in this study, nor has Adriamycin previously been found to be hepatotoxic. It is postulated that Adriamycin potentiated the hepatotoxicity of 6-mercaptopurine in these patients.