A multi-centre Australasian study of the efficacy of prophylactic ganciclovir in 88 recipients of marrow allografts at high risk for post-transplant cytomegalovirus (CMV) disease was conducted. The actuarial incidence of CMV disease was 10% in 74 recipients of HLA-identical family member transplants given ganciclovir but was 33% in 14 recipients of HLA-identical unrelated donor transplants given more immune-suppression pre- and post-transplant (P = 0.006). CMV disease developed in 4 of the 14 recipients of HLA-identical unrelated donor transplants at a median of 59 days post-transplant and was associated with concurrent graft-versus-host disease (GVHD) in 2 of the 4. CMV disease occurred in 5 of 74 recipients of an HLA-identical family member transplant at a median of 137 days post-transplant and was associated with concurrent moderate to severe GVHD in 4 of the 5. Thus the risk of CMV disease was higher in recipients who were not genotypically identical for HLA with their donors and who (in consequence) were given more immune-suppression than HLA-identical family member transplant recipients. Additionally, CMV disease can occur beyond the period of prophylactic ganciclovir administration (first 3 months post-transplant) in patients developing significant chronic GVHD and prophylaxis should be reintroduced at that time in such patients.