The influence of pretransplant herpes virus antibodies in patients and donors in the subsequent development of chronic graft-versus-host disease (GVHD) was analysed in 150 consecutive HLA identical bone marrow recipients. The Cox regression bivariate analysis showed that (i) pretransplant seropositivity for cytomegalovirus (CMV) in the patients and the donors, (ii) donor seropositivity for herpes simplex virus and Epstein-Barr virus, (iii) high donor and patient age, (iv) a previous grade II-IV acute GVHD, (v) patients receiving unirradiated donor buffy coat cells post-transplant, (vi) overall CMV infection, (vii) high donor herpes virus load (positive serology for 3-4 herpes viruses versus 0-2), and (viii) high recipient herpes virus load prior to BMT were all associated with a high incidence of chronic GVHD. In Cox regression multivariate analysis, high pretransplant donor herpes virus load (p less than 0.001) and a previous grade II-IV acute GVHD (p = 0.02) were the strongest predictors of chronic GVHD. Thus, herpes virus immune cells in the donated marrow may play a role in the pathophysiology of chronic GVHD.