Allogeneic haemopoietic stem cell transplantation can be complicated by acute graft-versus-host disease (GVHD). If the alloreactive T-cell clones responsible for this disorder could be identified before stem cell transplantation, they could be quantitatively monitored afterwards to allow initiation of immunosuppression before GVHD becomes apparent. We identified an alloreactive CD4+ T-cell clone from a donor before stem cell transplantation, and then monitored its frequency in the recipient's peripheral blood after transplantation by use of clonotypic quantitative real-time PCR. Greatly increased concentrations of this clone (nearly 100% of circulating CD4+ T cells) preceded and closely correlated with the onset of clinical GVHD, suggesting that a sole alloreactive T-cell clone was responsible for initiation of this disease in vivo. This simple identification and monitoring of potentially GVHD-causing clones can be undertaken before stem cell transplantation with no previous knowledge of the alloantigen responsible, and could allow earlier diagnosis and intervention in GVHD.