In vitro culture of T lymphocytes infiltrating solid tumors has resulted in populations with significant, and sometimes selective, anti-tumor activity. In this study we evaluated the ability of T lymphocyte populations generated from the marrow of patients with chronic myelogenous leukemia (CML) to suppress autologous hematopoietic progenitors. T lymphocyte populations were obtained by culture of CML bone marrow mononuclear cells (BMMNC) with low dose rIL-2 (25 U/ml) after initial PHA stimulation, and restimulation during culture with autologous marrow cells. Preincubation of the cultured CML T lymphocytes in close contact with autologous BMMNC resulted in significant, dose-related suppression of autologous CFU-MIX and BFU-E colonies (P < 0.001). Close contact between effectors and targets was important for progenitor suppression. Progenitor suppression was mediated by CD4-positive T lymphocytes. In contrast to the significant suppression of autologous progenitors by CML T lymphocytes, T lymphocytes from normal bone marrow did not suppress autologous progenitors. We conclude that T lymphocyte populations with significant autologous progenitor suppressing ability can be generated from CML marrow. These observations may be of therapeutic value in CML.