Arachidonic acid metabolites seem to play an important role in modulating the post-receptorial activity of interferon-alpha. In this study the effect of interferon-alpha on prostaglandin E2 production was evaluated in cultured liver tissue in 18 patients with chronic active hepatitis related to viral infection (9 hepatitis B virus (HBV) and 9 hepatitis C virus (HCV) positive) and in 7 uninfected patients with various liver diseases. The results show that interferon-alpha induces a significant increase in prostaglandin E2 production in both HBV and HCV chronic active hepatitis. Since the inhibition of the cyclooxygenase pathway increases antiviral protein synthesis and prostaglandin E2 has an immunosuppressive activity, this finding seems to suggest that a combined therapy (interferon-alpha plus non-steroidal anti-inflammatory drugs) should be indicated at least for patients who do not respond to interferon therapy alone.