The effects of malotilate, a hepatotrophic drug, on the inhibition of hepatocyte regeneration induced by ethanol were studied in rats. Following acute ethanol administration, both DNA synthesis and commencement of the S phase of the cell cycle in hepatocytes after partial hepatectomy were delayed. Malotilate prevents this ethanol-induced delay. Upon chronic ethanol administration, DNA synthesis after partial hepatectomy was reduced and commencement of the S phase was retarded. Treatment with malotilate clearly lessened the reduction in DNA synthesis in the resected liver, and retardation of the cell cycle was partially inhibited. These results indicate that malotilate prevents the ethanol-induced inhibition of hepatocyte regeneration at the dose tested and that this drug may be effective for the treatment of alcoholic liver disease.