Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in patients with chronic graft-versus-host disease (cGVHD), but the underlying mechanisms are not understood. The aim of this investigation was to determine whether humoral immune responses to the HCMV antigens were quantitatively different in hematopoietic cell transplant (HCT) recipients who developed cGVHD from those who did not. Antibodies to HCMV and its proteins UL94 and UL70 were quantitated in 79 cGVHD and 30 non-cGVHD patients by enzyme-linked immunosorbent assays (ELISAs). Mean levels of antibodies to the whole HCMV and to its protein UL94 were not significantly different between the cGVHD and the non-cGVHD subjects. However, the levels of antibodies to HCMV UL70 were significantly higher in non-cGVHD subjects than in those with cGVHD (20.91±15.63 versus 15.00±10.35 ng/mL; p=0.03). This suggests that anti-UL70 antibodies might play a protective role in the development of cGVHD.