Chronic hepatitis C virus (HCV) infection has been clearly established as a major risk factor in the development of hepatocellular carcinoma. In the present study we have attempted to identify the HCV genotypes associated with hepatocellular carcinoma in patients from the USA and Japan. RNAs from tumorous and non-tumorous tissues from 11 HCV seropositive Japanese patients, and plasma from 4 American patients were analysed by reverse transcription-polymerase chain reaction (RT-PCR) methods employing primers specific for the 5'UTR, the NS5 and E2/NS1 regions. Amplified products were cloned and compared by nucleotide sequencing and phylogenetic analysis. The 5'UTR region could be successfully amplified and sequenced from all samples, and phylogenetic analysis of the nucleotide sequences demonstrated with the exception of two of Japanese viruses were closely related to HCV type 1. Type 2 was detected in these two cases. In addition, two of the Japanese patients who were found to have cholangiocarcinoma were also found to be infected with type 1. HCV amplification of the NS5 was successful in 7 of the Japanese and 1 USA sample and clearly demonstrated that genotype 1b was predominant. Amplification of the E2/NS1 regions proved to be extremely difficult and was unsuccessful in all HCC patients despite the fact that these regions could be consistently amplified in samples from patients with both acute and chronic HCV infection. These findings might suggest that with long term persistent HCV infection, there may be marked heterogeneity in both the structural and non-structural regions of the virus, and/or possibly that the viral genomes may be defective.