Background: Increased serum leptin has been described after various organ transplants, with a mechanism that is still unclear., Methods: We measured serum leptin in 60 patients before and after allogeneic (allo) or autologous (auto) stem cell transplant (SCT) and in 60 healthy controls, matched for age and body mass index (BMI)., Results: Serum leptin was higher in patients after SCT than before and in controls. Leptin production was higher after allo- than after auto-SCT; the presence of chronic graft-versus-host disease (cGVHD) was associated with the highest values. The physiological correlation with BMI was lost in the allogeneic setting, indicating a strong influence of factors other than the nutritional status on circulating leptin. No relationship was found between serum leptin levels and time from transplant, age, cortisol, C-reactive protein, and T-lymphocyte CD4-to-CD8 ratio. Among the cytokines secreted by type-1/type-2 T-helper lymphocytes, only serum interferon-gamma significantly correlated with serum leptin levels. Anti-leptin blocking antibodies partially inhibited T-cell activation in mixed lymphocyte reaction, suggesting a link between leptin and T-lymphocyte activation in the allo-SCT setting., Conclusion: Taken together, these findings suggest that increased serum leptin concentrations may contribute to T-cell activation during development of cGVHD.