The nuclear matrix proteins (NMPs) consist of common and tissue-specific nuclear proteins, which can be altered by extracellular environments such as radiation, chemicals and virus infection. Thus, NMP profiles were analyzed in diethylnitrosamine (DEN)-treated rat liver. Male F344 rats (6 weeks old) were treated continuously with DEN (40 ppm) in drinking water. All animals were sacrificed at 10, 20 or 30 weeks during the experiment. The profiles of NMPs and cytoskeletal proteins (CSPs) progressively changed in their number and amount in DEN-treated rats. Four peptides increased in their relative amounts, while three decreased in the 10- and 20-week groups. Many NMPs were detected in DEN-induced hepatocellular carcinomas. These results suggest that the alteration of the NMPs may be involved in DEN-induced hepatocarcinogenesis.