HBsAg bound to IgM was detected in serum of HBsAg carriers with a radioimmunoassay based on selective absorption of the immunoglobulin on a solid phase coated with antiserum to human IgM. High titers of HBsAg/IgM were found in sera with the highest HBsAg binding capacity of polymerized human serum albumin (poly-HSA) and of C1q. These findings and the inhibition of HBsAg/IgM reaction by addition of purified poly-HSA suggest that the IgM component of the complex might bind to poly-HSA fixed on to HBsAg particles and possibly represent antibody to the modified plasma protein. HBsAg/IgM was detected in 95 (87%) patients with acute HBsAg positive hepatitis during the acute phase of infection and persisted after the fourth week only in patients who developed chronic liver disease. HBsAg/IgM were detected in one out of 15 carriers of the HBsAg with superimposed Non B hepatitis. HBsAg/IgM were also present in 76% to 100% of sera from chronic carriers without any relation to the extent of viral replication and to presence of severity of liver disease. Persistence of HBsAg/IgM in patients with acute hepatitis B may provide a useful tool to predict transition of HBV infection to chronicity.