Recently, GBV-C and HGV-two isolates of the same new flavivirus-were identified in serum samples of patients with indeterminate hepatitis and posttransfusion hepatitis, respectively. The pathogenic relevance of these viruses is still uncertain. As viral infections are presumed to trigger autoimmune processes, we investigated GBV-C in autoimmune hepatitis as well as in cryptogenic hepatitis, and compared the prevalences to patients with chronic viral hepatitis and those of blood donors. We found only a slightly higher prevalence of the virus in cryptogenic (12%) and autoimmune hepatitis type I-III (6.7%, 10%, and 12.5%) compared to blood donors (4.7%). In contrast, patients with viral hepatitis B, C, and D were more frequently infected with GBV-C (16%, 20%, 36%). These results suggest that GBV-C is not a major cause for inducing autoimmunity and leading to autoimmune hepatitis. We analyzed the nucleic acid sequences of a representative number of GBV-C positive patients (24/42) and found a broad range of nucleotide similarity in the NS3 helicase region (74-100%) among the isolates and the prototype sequences. However, we could not identify a specific sequence, which would point to a certain strain or subtype of the virus associated with autoimmune or cryptogenic liver disease.