To document the prevalence and routes of transmission of SEN virus (SEN-V) in community-based individuals and patients referred to a liver disease unit, stored serum samples obtained from 160 Canadian Inuit and 140 patients with liver disease were tested for SEN-V DNA by polymerase chain reaction. In the community-based population, SEN-V was present in 57 (36%) of 160 persons. SEN-V-positive individuals tended to be younger and were more often male. Liver enzyme levels and serologic markers for hepatitis A and B viruses were similar in SEN-V-positive and SEN-V-negative individuals. SEN-V was present in 30 (21%) of the 140 patients with liver disease. Age, sex, risk factors for viral acquisition, prevalence of symptoms, and liver biochemical and histological findings were similar in SEN-V-positive and SEN-V-negative patients. These results indicate that SEN-V infection is a common viral infection in both healthy individuals and patients with chronic liver disease, that transmission likely occurs via nonparenteral routes, and that SEN-V infection is not associated with higher rates of or more-severe liver disease in persons with preexisting liver disease.