The cumulative incidence of chronic graft-versus-host disease (GVHD) was 48% among 165 patients with severe aplastic anemia who had been discharged from Seattle 3 months after they were treated with marrow grafts from HLA-identical siblings. Estimated 10-year survival was 85%. Preceding acute GVHD had a dominating influence on the development of chronic GVHD. Almost all patients with grades II-IV and 67% of those with grade I acute GVHD developed chronic GVHD. Among patients without previous acute GVHD, three factors were independently correlated with an increased risk of de novo chronic GVHD: increasing patient age, the infusion of buffy coat cells in addition to the marrow, and corticosteroid therapy before transplantation. For example, patients below and above age 20 years who had neither buffy coat cell transfusions nor preceding corticosteroid therapy had an incidence of chronic GVHD of only 4-8%, while those with either buffy coat cell transfusions or corticosteroids or both had incidence rates of 33-70%. The development of chronic GVHD significantly influenced survival. Among 83 patients without chronic GVHD, only one died (on day 150 with interstitial pneumonia), compared to 23 deaths among 82 patients with chronic GVHD. For results of marrow grafting for aplastic anemia to improve, better prevention of chronic GVHD is needed.