Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.