A sensitive radioimmunoassay was developed for specific detection of IgM antibodies to the hepatitis b virus-associated delta antigen. The test is based on the selective absorption of IgM by anti-IgM fixed on a solid phase. Transient primary IgM anti-delta responses with no conversion to a secondary IgG response were observed in acute self-limited delta infection. IgM anti-delta was invariably found in hepatitis B surface antigen (HBsAg) carriers with active delta infection and liver disease, while it was absent in HBsAg-positive or negative individuals with anti-delta of IgG class but without liver damage or intrahepatic delta antigen. IgM anti-delta appears useful in defining the epidemiology of acute delta infection and in the serological diagnosis of active delta disease from nonpathogenic or past delta infection.