We analyzed factors associated with the development of chronic graft-versus-host disease (GVHD) in 469 consecutive patients receiving matched sibling allogeneic bone marrow transplantation (BMT). Overall, 41 +/- 6% (95% confidence interval) developed chronic GVHD between 2 and 50 months after BMT. Multivariate analysis showed that previous acute GVHD was the dominant independent risk factor predisposing to chronic GVHD (Relative Risk 4.82, p < 0.0001). In addition, recipient age of > or = 18 years and male recipient with female donor were also independent predictive factors for development of chronic GVHD. When acute GVHD and recipient age were considered, groups with distinctive risks of chronic GVHD were identified. Patients under 18 without previous grade II-IV acute GVHD had only a 10 +/- 5% risk of chronic GVHD. Patients over 18 with no prior grade II-IV acute GVHD had a 31 +/- 12% risk while patients with advanced acute GVHD, regardless of age, had the highest risk and 70 +/- 8% developed chronic GVHD. It is important to consider these factors when designing and assessing clinical trials of chronic GVHD prophylaxis and treatment.