The recently identified hepatitis G virus (HGV, also named GB virus-C, GBV-C) appears to have similarities to hepatitis C virus and other flaviviridae. To better understand its clinical significance and hepatotropism, we collected liver tissue and matched serum samples from 56 patients undergoing liver transplantation. HGV/ GBV-C RNA was detected by reverse transcription-nested PCR, using primers from the relatively conserved 5' noncoding region of the genome to detect HGV/GBV-C RNA and the amount was semiquantitatively estimated by serial 10-fold endpoint dilution. The presence and amount of HCV RNA was estimated by the same methodology. Seventeen patients (30%) had HGV/GBV-C RNA detectable either in liver or in serum, including two of three with cryptogenic liver disease. Interestingly, 5 of 17 (29%) patients had HGV/GBV-C RNA in serum but not liver, even with repeated testing of hepatic RNA from different portions of the liver. Furthermore, the titer of HGV/GBV-C RNA was significantly lower in liver than in serum in most samples (mean log titer, 1.33 vs. 2.56, P < 0.05). In contrast, all 21 patients with HCV RNA in serum also had the virus detectable in liver. In five patients coinfected with HCV and HGV/GBV-C, the mean titer of HCV RNA in liver was higher than that in serum (log titer, 2.8 vs. 3.0, P > 0.05). Thus, our results suggest that HGV/GBV-C is probably not hepatotropic and may replicate predominantly in sites other than the liver. These findings brings into question the role of HGV in causing significant liver disease. J. Med. Virol. 58:160-164, 1999. (C) 1999 Wiley-Liss, Inc.