AIM: To investigate the prevalence of hepatitis G virus (HGV) infection and to analyse the homology of different HGV strains in Southern China. METHODS: A total of 1993 sera from different groups in Guangdong, Hong Kong, and Yunnan were detected by reverse transcription polymerase chain reaction (RT-PCR). The nucleoticle sequences of 5'untranslated region (5'UTR) derived from 20 strains and NS5 region from 3 strains were determined. RESULTS: The positive rate of HGV RNA was 0.89 % in community population, 2.57 % in blood donors, 17.86 % in intravenous drug abusers, 14.13 % in patients with hemodialysis, 13.66 % in those with hepatocellular carcinoma, 25.30 % in non A-E hepatitis, 7.22 % in hepatitis B, 12.73 % in hepatitis C, 41.67 % in patients received bone marrow transplantation, respectively. The homology was 90.40-100 % in 5'UTR among different strains, while that of NS5 region was 93.3-94 % in nucleoticle sequence, and 97-99.2 % in amino acid sequence. CONCLUSION: These results showed that there was a high incidence of HGV infection in patients from Southern China, being treated for bone marrow transplantation, hepatocellular carcinoma and those on haemodialysis. Furthermore, there was also a high frequency of co-infection of HGV with HBV, HCV, non A-E viral hepatitis and that among intravenous drug abusers. The study also showed that sequence variation in different strains was associated with geographical factors but there was no significant difference in 5'UTR in circulating viruses between different patient groups. Finally, by sequential analysis of viral species present in individual patients over a three months period there was no evidence of sequence variation in the 5'UTR.