Antibodies to cytokeratin (CK) are found in some patients with autoimmune hepatitis (AIH). We hypothesized that serum antibodies to CK8, CK18 and CK19 may be formed in patients with AIH. We established an enzyme-linked immunosorbent assay (ELISA) to quantify anti-CK8, anti-CK18 and anti-CK19 antibodies in sera of patients with AIH. In addition, we quantified circulating CK8:anti-CK8 antibody as well as CK18:anti-CK18 antibody immune complexes in patients' sera, by an enzyme-linked immunosorbent assay (ELISA). Furthermore, to evaluate the expression of CK8, CK18 and CK19 in liver tissue, immunohistochemical stainings were performed. Significantly high levels of anti-CK8, anti-CK18 and anti-CK19 antibodies were demonstrated in patients with AIH compared with normal volunteers and patients with chronic active hepatitis C (CH-C). In addition, these antibodies were significantly decreased after steroid treatment. Levels of CK8:anti-CK8 and CK18:anti-CK18 immune complexes in sera of patients with AIH were significantly high compared with those of patients with CH-C and normal volunteers. Immunohistochemically, CK8 or CK18 were absent from some hepatocytes of AIH. CK19 was aberrantly expressed in periportal hepatocytes in patients with AIH, but not CH-C. This is the first study to quantify anti-CK8, anti-CK18, anti-CK19 antibodies and immune complexes in patients with AIH. The clinical significance of anti-CK antibodies and their immune complexes of AIH is also discussed.