Graft-versus-host disease (GVHD), a common complication of hematopoietic stem cell transplant, is generally regarded to develop through cell-mediated immune response following activation of helper T cells. Since production of antibodies is also mediated by helper T cells, the role of humoral immunity in GVHD is questioned and has not yet been explored in clinical practice. We conducted a pilot study to evaluate the role of antibody production in hepatic H-GVHD and whether it can distinguish acute and chronic forms.C4d expression was increased in portal vessels and hepatic sinusoids of patients with histological proven evidence of GVHD 11/16 (P=0.007). Patients classified as chronic GVHD were statistically more likely to have C4d expression in the portal vasculature and liver sinusoids (P=0.011).Humoral activation seems to play a role in pathophysiology of hepatic, especially chronic GVHD.