Immune thrombocytopenic purpura (ITP) in childhood is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Although generally considered to involve autoreactive B lymphocytes which produce antiplatelet antibodies, there is increasing evidence that T lymphocytes also play an important role in this autoimmune process. We studied 11 children with acute ITP and 19 children with chronic ITP and observed elevated numbers of TCR gamma delta+ T lymphocytes in several patients. In the three children with the highest elevations (TCR gamma delta+/CD3+ percentage ranging from 37.8 to 48.1% at initial evaluation), the expanded cell population exclusively expressed the surface V delta 2/V gamma 9 heterodimer and had enhanced in vitro proliferation to mycobacterial extracts and IL-2. Analysis of the nucleotide sequences used by these TCR gamma delta+ cells demonstrated a diverse set of VDDJC gene rearrangements, indicating polyclonal expansion of cells reminiscent of a superantigen response. There was a close correlation between the number of TCR gamma delta+ T lymphocytes and the degree of thrombocytopenia in each patient. TCR gamma delta+ T lymphocytes may be important in the pathogenesis of immune-mediated platelet destruction in some children with ITP.