The relationship between CCl4 or (CCl4 + phenobarbital)-induced liver cirrhosis and diethylnitrosamine (DEN) hepatocarinogenesis in male F-344 rats was investigated. DEN given alone produced no liver lesions after 16 weeks, but 4/12 (33%) neoplastic nodules developed when nitrosamine was administered to rats with previously established cirrhosis. On the other hand, (CCl4 + phenobarbital) post-treatment had an even stronger effect, increasing the yield of neoplastic nodules to 100% (28/28). Since the exposure time of DEN was the same in all treated groups (4 months), the results indicate the decreased effectiveness of(CCl4 + phenobarbital) pretreatment on DEN hepatocarcinogenesis.