The changes in cytokeratin (CK) intermediate filaments (IFs) of the hepatocytes in the hyperplastic nodules (HNs) of the rat's liver developed by Solt and Farber's model were studied by light and electron microscopy, immunofluorescence (IMF), immunoelectron microscopy (IEM) and immunoblotting (IMB). Frozen sections of liver tissues were extracted by Triton X-100 and nuclease. IEM was performed by using monoclonal anti-CK antibody (PKK1: CK55 and CK49). CK staining by IMF was markedly decreased in the hepatocyts in HNs compared with that in the parenchyma surrounding HNs; however, IEM clearly showed a lot of non-staining IFs in hepatocytes in HNs. In the IMB, two bands in insoluble proteins extracted from control rat liver and the experimental rat liver including HNs reacted with CK55 and CK49, respectively. These findings indicate that immunocytochemical change of IFs of hepatocytes might be occurred in the precancerous lesion of the experimental hepatocarcinogenesis in rats.