To investigate mitogen induced helper interleukin 2 (IL-2) production in patients with chronic liver disease (CLD), IL-2 activity was assessed by an IL-2 bioassay using phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMNC). IL-2 activity was significantly reduced in patients with autoimmune chronic active hepatitis, primary biliary cirrhosis and alcoholic hepatitis with or without cirrhosis (P less than 0.01), and was comparable to controls in those with alcoholic cirrhosis alone. In vitro preincubation of PBMNC with lymphoblastoid alpha-interferon (alpha-IFN) before stimulation with PHA, led to a significant increase in IL-2 activity in all subjects (P less than 0.01), except those with alcoholic hepatitis, but in none of the groups did the levels of IL-2 activity reach those seen in normal subjects. The decrease in IL-2 activity in patients with CLD may be due to low IL-2 production or presence of an IL-2 antagonist(s). Such an abnormality may occur, not only as a result of liver damage, but may also be important in determining immunological disturbances involved in the pathogenesis of the liver disease.