Immunological factors seem to be important in determining the course and outcomes of both acute and chronic viral hepatitis. Furthermore, promising therapies for chronic viral hepatitis have profound effects on immune function and sustained responses to therapy may depend largely on restoration of normal immune responsiveness. The role of immunologic mechanisms in determining the course and ultimate outcome of viral hepatitis is being studied. Cytokine mRNAs were determined using a reverse transcriptase (RT) PCR technique in liver biopsies from 14 patients with HBeAg positive chronic hepatitis B and 6 normal subjects (transplantation donors). Only one of the control biopsies was positive for 2 of the 7 mRNAs assayed. In contrast, there was a high prevalence (43-80%) of detectable mRNAs for IL-1, IL-2, IL-4 and IFN-gamma in chronic hepatitis B. mRNAs for IL-5, IL-6 and TNF-alpha were not prevalent in chronic hepatitis B. Quantitative RT-PCR revealed that high levels of mRNA for IL-4 and IFN- gamma correlated with severe inflammation, suggesting that the production of IL-4 and IFN-gamma may be important in tissue injury in the liver in chronic hepatitis B with active viral replication.