Patients with classical hemophilia (hemophilia A) and Christmas disease (hemophilia B) were exposed to many hepatotropic viruses during the course of their therapy. Severe chronic hepatitis among these patients was most likely related to persistent infection with non-A, non-B hepatitis virus, hepatitis B virus, or delta hepatitis virus, a defective RNA virus which is dependent upon coinfection with HBV for essential helper functions. Carriers of HBV could contract an acute delta hepatitis infection that was invariably more severe than the illness caused by HBV alone. The morbidity and mortality of delta hepatitis infection was remarkably high. Transmission of the delta hepatitis agent appeared to follow the same routes of transmission as HBV. Direct parenteral inoculation was the classic mode of transmission of HBV which suggested a similar mode of transmission for delta hepatitis.