Inoculation of hepatitis B surface antigen (HBsAg)-positive sera from patients with chronic liver disease and intrahepatic delta (δ) into chimpanzees susceptible to infection with hepatitis B virus (HBV) resulted in type B hepatitis and δ markers (δ antigen and antibody to δ) in recipient animals. A dilution (10^-8) of serum induced type B hepatitis without δ markers in another HBV-susceptible animal. HBV infection and δ markers did not develop in animals with preexisting titers of antibody to HBsAg. In chimpanzees with circulating HBsAg at the time of inoculation, synthesis of d occurred earlier and its extent and duration were greater than in animals previously unexposed to HBV; coincident with synthesis of δ, hepatitis occurred in chronic HBsAg carriers, and synthesis of preexisting HBV gene products (HBsAg and hepatitis B core antigen) was diminished. Delta appears to be a marker of a transmissible pathogenic agent, either an HBV variant or another agent that requires the helper functions of HBV, that is defective and interferes with HBV replication.