We found a significant increase of activated circulating T lymphocytes expressing interleukin 2 receptor (IL-2r) (mean +/- s.e.m. 11.0 +/- 1.1%) or DR antigen (5.0 +/- 0.49%) in patients with autoimmune chronic active hepatitis (CAH) starting in childhood when compared to healthy controls (0.14 +/- 0.09%, P less than 0.001 and 2.8 +/- 0.06%, P less than 0.01). Patients with liver disorders due to Wilson's disease (IL-2r 0.64 +/- 0.25%, DR 3.5 +/- 0.22%) or alpha-1-antitrypsin deficiency (IL-2r 0.1 +/- 0.06%, DR 2.8 +/- 0.35%) had levels similar to controls. Levels of both IL-2r and DR positive T lymphocytes were higher in patients with uncontrolled CAH (IL-2r 18.0 +/- 1.01%; DR 6.3 +/- 0.78%) than in patients with inactive disease (IL-2r 3.2 +/- 1.4%, P less than 0.001; DR 3.0 +/- 0.13%, P less than 0.01). In patients with active disease levels of IL-2r positive cells were higher than DR positive cells (P less than 0.001). Only 21% of activated T cells coexpressed the two markers of activation. Sixty-seven percent of IL-2r positive T lymphocytes were helper/inducer and 25% suppressor/cytotoxic, while 66% of the DR positive T cells were suppressor/cytotoxic and 31% helper/inducer. The finding that the highest levels of activated T lymphocytes are present in patients with uncontrolled CAH suggests that these cells are involved in its pathogenesis. The preferential increase of activated helper/inducer cells might explain the enhanced immune reactivity characteristic of autoimmune CAH.