We have analyzed the presence of IgG and IgM anti-calmodulin antibodies (anti-CaM) by ELISA in patients with chronic hepatitis due to B, δ and C viruses as well as in patients with other liver diseases. The specificity of the assay was demonstrated by pre-adsorption of positive serum with calmodulin (CaM) but not with myosin light chain. Among 164 patients whith chronic viral hepatitis (B, δ and C) and 50 with non-viral hepatitis, 27 and 26%, respectively, had auto.antibodies against CaM. There was a significantly increased frequency (37%) of these auto-antibodies in chronic δ infection as compared to that (21%) of patients with chronic B hepatitis (p < 0.05). An intermediate incidence of anti-CaM, (24%) was found in chronic C infection. The frequency of anti-CaM was not related to the level of hepatitis B virus (HBV) or hepatitis δ virus (HDV) replication. A high occurrence of anti-CaM in the presence of liver membrane antibody (p < 0.03) was observed. During follow-up of patients with chronic δ-hepatitis, the presence of anti-CaM was consistently observed, when the isotype was IgM, but transiently when it was IgG. The occurrence of anti-CaM correlated neither with ALT levels nor with histological diagnosis. Antibodies to CaM, are present in liver diseases especially in chronic δ-hepatitis, and do not play a pathogenic role on hepatocellular d