The freeze-fracture technique has been used to study the organization of intercellular junctions in two cases of hepatocellular carcinoma. A tumor free cirrhotic liver has been included for comparison. Tight junctions were disorganized in the tumor cells of hepatocellular carcinoma. The tight junction networks often were not orientated parallel to the canalicular lumen. In some areas tight junctions comprised 2 to 4 strands, while in other areas they were reduced to a single strand. Discontinuities and local proliferation of tight junctions were also seen. Some tight junctions were composed of intramembrane particles aligned to form a discontinuous network. Gap junctions between the tumor cells were small and infrequent. Gap junctions were found only on the lateral plasma membranes and were not seen within the tight junction networks. These findings have been interpreted to indicate changes in intercellular communication, and an alteration in the ability of hepatocytes to differentiate tight junctions in hepatocellular carcinoma.