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Several studies from Europe have observed a relationship between hepatitis C virus infection and anti-liver/kidney microsome-1 (anti-LKM-1) positive chronic hepatitis. It has been suggested that hepatitis C may induce an autoimmune phenomenon that leads to the development of a specific type (type II anti-LKM-1 positive) autoimmune chronic hepatitis. We evaluated 204 sera from patients with well-documented hepatitis C infection from two centres in the United States of America and compared them with sera from 428 French patients from three centres. We evaluated the serological prevalence of anti-smooth muscle antibodies, anti-nuclear antibodies, anti-liver cytosol antibodies, and anti-mitochondrial antibodies subtype anti-M2 in patients with chronic hepatitis C. The two groups were matched in their ages, gender, mode of transmission of hepatitis C infection and severity of liver disease. Anti-LKM-1 was not observed in the patients from the USA at a time when it was noted in 3.7% of French patients. There were no differences, however, in the expression of other auto-antibodies, which were often in low titres. Absence of anti-LKM-1 in USA sera in comparison with French sera suggests that there may be differences in induction of anti-LKM-1 related to environmental and/or host genetic factors, and/or genomic variation in the hepatitis C virus.