Hepatitis virus infections are frequent in patients suffering from HIV infection due to similar transmission routes of these viruses. In addition, hepatitis virus infections lead to impaired survival in HIV positive patients. The recently discovered flavivirus GB virus C (alias Hepatitis G Virus) was initially believed to be another hepatitis virus. While there is still some minor discussion whether GB virus C (GBV-C) plays a role in fulminant hepatic failure, there is no evidence that this virus is responsible for chronic liver disease. Thus this 'orphan virus' still seeks its disease. In this review we concentrate on the published data concerning the co-infection of GBV-C and HIV. By summarizing the studies available, we show evidence for a beneficial influence of GBV-C on HIV infection. Many studies demonstrated a high prevalence of GBV-C infection in HIV positive patients due to its parenteral and sexual transmission. However, in contrast to the expectations, GBV-C does not aggravate the course of patients suffering from HIV infection. Even though not uniformly found, one often sees higher CD4 counts in patients with ongoing GBV-C viral replication. Likewise, a lower viral load appears to be accompanied by the presence of GBV-C RNA in the serum. In addition, longitudinal studies indicate that GBV-C infection slows down the progression to AIDS and eventually to death. GBV-C probably influences HIV infection associated disease by either directly inhibiting HIV replication or enhancing the immune competence to cope with HIV. Still the definitive mechanism how GBV-C could inhibit the progression to AIDS and eventually death needs to be identified. (C) 2001 Published by Elsevier Science B.V.