Recently, a novel DNA virus designated SEN virus (SEN-V), which is thought to be related to posttransfusion hepatitis, was discovered. The aim of the present study was to clarify the relationship between SEN-V infection and the development of liver disease. We examined SEN-V from the sera of 21 patients with non-B, non-C hepatocellular carcinoma (HCC) and 13 patients with non-B, non-C chronic liver disease (CLD) without HCC who were admitted to our hospital between 1995 and 1997. Thirty-two patients without liver disease served as controls and were also examined for SEN-V. SEN-V DNA was detected by the nested PCR method after extraction of DNA from serum. SEN-V DNA was detected in 74% (25 of 34) of patients with CLD with or without HCC who were negative for both hepatitis B virus surface antigen and anti-hepatitis C virus antibody. SEN-V DNA was detected in 69% (9 of 13) of CLD patients without HCC and in 76% (16 of 21) of HCC patients. The prevalence of SEN-V was no higher in patients with liver disease than in patients without liver disease (24 of 32; 75%). There were no significant differences in age, sex, liver function, history of blood transfusion, or amount of alcohol intake between SEN-V-positive and SEN-V-negative CLD and HCC patients. Genetic analysis suggested that SEN-V is closely related to the TT virus family. SEN-V was detected at almost the same frequency in patients with and without liver disease. SEN-V does not seem to contribute either to the pathogenesis of liver disease or to the development of HCC from chronic liver disease.