Abstract: CD40 ligand (CD40L) is expressed not only on activated T cells but also on activated platelets. A soluble CD40 ligand (sCD40L) is released from the activated T cells and platelets by ill-defined proteolytic process in vitro. It has been reported that sCD40L is elevated in the serum of patients with systemic lupus erythematosus, unstable angina, essential thrombocythemia, and autoimmune thrombocytopenic purupura. However, source of sCD40L in vivo remains to be elucidated. We investigated the serial sCD40L in the serum in patients undergoing allogeneic stem cell transplantation and compared with the platelets number and soluble IL2R, which is a marker of activated T cells. The value of sCD40L was well correlated with platelet number or thrombopoiesis. In cases of severe graft vs. host disease with markedly increased sIL2R, sCD40L was not increased in vivo. These results indicate that sCD40L in vivo is released mainly from the platelets or in the process of platelet production but not from the activated T cells.