BACKGROUND/AIMS: Molecular and structural studies of hepatitis C virus (HCV) replication and infection have been performed on cultured cells and on serum of infected patients. No conclusive studies were conducted yet on human liver biopsies. This paper describes the ultrastructural findings of hepatitis C virus components in liver biopsies. METHODS: Liver specimens from acutely and chronically HCV-infected chimpanzees (five each) and 29 chronic hepatitis C patients were studied. Diagnosis of HCV infection was based on clinical, serological, light microscopic and immunohistochemical data and on HCV RNA polymerase chain reaction. RESULTS: In HCV-infected chimpanzees, tubular aggregates were observed in the cytoplasm of a significant number of hepatocytes and proven by immuno-electron microscopy to contain HCV-E2 viral envelope material. Identical tubular aggregates were seen in hepatocytes of chronic HCV-infected patients, although in smaller quantity and less frequently. A few single enveloped virus-like particles of 50-60 nm in diameter were seen for the first time in the hyaloplasm of hepatocytes of HCV-infected chimpanzees and patients. CONCLUSIONS: For the first time, HCV envelope material was ultrastructurally identified in hepatocytes of HCV-infected chimpanzees and patients. Virus-like particles, although strongly suggestive for HCV, failed final confirmation at least by routinely used methods.