The proliferation and differentiation of donor hematopoietic progenitor cells in bone marrow transplantation (BMT) recipients is influenced by hematopoietic growth factors, which could derive from either T cells or adherent stromal bone marrow cells, or both. In this study of 20 BMT recipients, we asked whether T lymphocytes arising from donor bone marrow grafts were able to express normal levels of granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA, and to secrete normal levels of soluble GM-CSF in response to the mitogen phytohemagglutinin. We have found that T cells obtained up to 18 months following BMT express little or no PHA-induced GM-CSF message. T cell GM-CSF secretion in response to PHA is also reduced or absent. This T cell GM-CSF defect was observed in all patients studied, whether or not donor bone marrows had undergone T cell depletion. This defect likely reflects a broader deficit in mitogen-induced lymphokine production. This defect likely contributes to BMT recipients' blunted responses to infections, and contributes to graft failure in T cell-depleted transplants.