The study was conducted collaboratively within the seven hemophilia treatment centers which comprised the Southeastern Hemophilia Group. Upon entry into the study, patient data were collected on transfusion and factor concentrate therapy, age, race, type of hemophilia, sex, homosexuality, drug abuse and HTLV-III antibody status. Liver function was assessed noninvasively. Since available tests for HDV infection had limited sensitively and were not necessarily specific for HDV persistence, HDV RNA was detected in serum by molecular hybridization using cloned HDV cDNA and single-stranded RNA probes. Western blot analysis was used to assess antibody responses to HDV. A multifactorial analysis of clinical and virological data was conducted at the end of the first year of the study. Patients were reevaluated clinically and virologically at six month intervals to ascertain risk factors for acquisition of HBV and HDV infections, and to assess the prevalence and rate of progression of liver disease in each group. Follow-up of patients who had not been previously transfused, allowed an assessment of the efficacy of current control measures such as HBV immunization and use of heat-treated factor concentrates for prevention of viral infections in hemophiliacs.