Chimpanzees were inoculated intravenously with the H strain of hepatitis C virus (HCV), and analysed for viraemia using the polymerase chain reaction and for a humoral immune response using first and second generation anti-HCV ELISAs and an immunoblot assay (4-RIBA). In all seven chimpanzees studied, viraemia occurred several weeks before a significant increase in serum alanine transferase (ALT) activity, whereas the first circulating anti-HCV antibodies became detectable at the time of significant increase in ALT levels, provided the second generation ELISA or 4-RIBA was used. On the basis of the duration of viraemia the chimpanzees studied could be assigned to two different groups: those in which viraemia disappeared in conjunction with or shortly after seroconversion, and those remaining viraemic for many weeks after the appearance of antibodies. The clearance of HCV from the circulation did not correlate with the antibody pattern determined using 4-RIBA, i.e. the HCV-specific assays currently available do not enable us to predict whether an infected chimpanzee will develop persistent viraemia. Only two of the seven chimpanzees analysed developed anti-core protein (c-22) antibodies, which appeared at the same time as the first ALT peak, whereas all animals developed antibodies to the non-structural protein, c-33, and these antibodies persisted.Only after the hepatitis C virus (HCV) genome had been cloned by Choo et al. (1989) was it possible to develop specific assays, such as ELISA, recombinant immunoblot assay (RIBA) and the polymerase chain reaction (PCR), to diagnose HCV infection. These assays can now be used to study the development of viraemia and the specific immune response in HCV-infected chimpanzees, the only experimental animals sensitive to HCV. Shimizu et al. (1990) published a study on the early stages of HCV infection in chimpanzees, focusing on the determination of viraemia by PCR. Their study of the humoral immune response was limited to the first generation assay, detecting antibodies to c-100 only, a recombinant polypeptide that represents part of a nonstructural HCV protein.We have extended these studies on HCV viraemia and the specific immune response in chimpanzees using the assays developed most recently. The seven animals investigated were positive (HCV-infected) controls from studies in which the inactivation of HCV by various methods included in the procedures for manufacturing human plasma proteins for therapeutic use had been studied (Mauler et aL, 1987). The HCV isolate used for spiking the source plasma preparations in these studies was the human H pool plasma, now designated H strain (Ogata etal., 1991). Chimpanzees inoculated with HCVspiked human plasma or plasma derivatives were regarded as being HCV-infected when the serum alanine transferase (ALT) activity increased significantly, and infections with hepatitis A virus (HAV), hepatitis B virus (HBV) and the human herpesviruses, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), could be excluded.We demonstrate that the chi...