Objective To investigate pathogene city, replication and expression of hepatitis G virus (HGV) in rhesus monkey infected with HGV RNA genome or HGV RNA positive sera. Methods A full length cDNA clone of HGV was constructed. Rhesus monkey BY1 was inoculated intrahepatically with genomic RNA from this HGV clone resulted in viral replication. HGV RNA positive sera from BY1 were intravenously inoculated into rhesus monkeys BM1, and sera from BM1 were intravenously inoculated into BB1 in series. Sera were collected weekly or bi weekly and liver biopsies were performed regularly. RT PCR, in situ hybridization and immunological, serological, histological assays were carried out to study the infectivity and pathogenecity of HGV. Results The serological and pathological results indicated that all of the 3 rhesus monkeys developed HGV viremia and had slightly elevated alanine transaminase levels (up to 418 IU/ L) during the period of experiment. HGV RNA became positive at the 3 rd , 8 th and 3 rd week post inoculation in the animals BY1, BM1 and BB1 respectively, and existed up to 21 weeks. The histology, immunohistochemnistry, and in situ hybridization in the liver tissues of the inoculated animals also showed that there was a mild hepatitis with HGV E2 expression in cytoplasm of hepatocytes. RT PCR and quantitative PCR showed that HGV could replicate in liver.Conclusions The genomic RNA from HGV full length cDNA is infective to the rhesus monkeys resulting in mild hepatitis. Infection and the transmission of the HGV in the rhesus monkey provide an appropriate animal model for the study of HGV.