Cellular immunity to hepatitis-B-virus (HBV) antigens was followed prospectively in five patients who were identified in the early incubation phase of acute HBV infection, between 30 and 70 days before the onset of liver damage. Cellular immunity to pre-S antigens was the first detectable immune response, appearing 30 days before the first rise in serum aminotransferases in every case. T-cell sensitisation to HBcAg followed, with IgM anti-HBc appearing 10 days later. A cellular immune response to HBsAg was the last to appear, 10 days before the onset of liver damage. These cellular immune responses are the earliest host responses to the virus infection and could be critical in initiating and directing the processes of liver damage and viral clearance.