The cytostatic Adriamycin and the herbicide paraquat form reactive oxygen species during enzymatic activation. Adriamycin, but not paraquat, is also able to intercalate into DNA and to interfere with DNA synthesis and transcription. We investigated the influence of both substances on antioxidant enzyme expression in primary rat hepatocytes. Treatment of hepatocytes with Adriamycin led to an increase in catalase and a decrease in MnSOD mRNA expression. In contrast, exposure of hepatocytes to paraquat resulted in an increase in both catalase and MnSOD message levels. CuZnSOD mRNA was not responsive to either treatment. Adriamycin almost completely inhibited RNA synthesis, but paraquat did not change either RNA or protein synthesis. Both substances induced lipid peroxidation as measured by the accumulation of malondialdehyde in the medium. These findings indicate that catalase and MnSOD are not regulated coordinately in hepatocytes and that ROS-producing agents can differentially influence expression of antioxidant enzymes depending on their capacity to inhibit transcription.