We analyzed the incidence and risk factors for chronic graft-versus-host disease (GVHD) in 265 children undergoing allogeneic stem cell transplantation (SCT) who survived longer than 3 months post SCT. Patients transplanted from HLA-mismatched related donors and matched unrelated donors were included. Fifty-five patients developed chronic GVHD between 1 and 25 months after SCT, and the 5-year cumulative incidence of chronic GVHD was 22%. By multivariate analysis, acute GVHD (P = 0.004), malignant disease (P = 0.004), recipient age (> or =10 years) (P = 0.01) and a female donor to male recipient (P = 0.035) were significant risk factors for chronic GVHD. When acute GVHD was excluded from the multivariate analysis, malignant disease (P = 0.002) and older recipient age (P = 0.007) were identified. The incidence of chronic GVHD in this childhood study was lower than that observed in adults, and recipient age was an important factor in childhood SCT. The high incidence associated with malignant disease may be affected by changes in GVHD prophylaxis in order to ensure graft-versus-tumor effects.