To study the effect of acute and chronic graft-versus-host disease (GVHD) on recurrent leukemia, we analysed data on patients with acute leukemia receiving allogeneic marrow transplants in Seattle between 1970 and 1986. Four hundred fifty-four patients survived in remission 150 days after HLA-identical transplant and 114 currently survive five to fifteen years after marrow grafting. At the time of transplant, 252 patients had acute nonlymphocytic leukemia in remission or relapse and 202 had acute lymphocytic leukemia in remission or relapse. According to Kaplan-Meier estimates, recurrence of leukemia following transplantation was observed in 28% of patients developing moderate to severe (grade II-IV) acute GVHD and 48% of patients with no or mild (grade O-I) acute GVHD (p = 0.0028). Relapse was observed in 34% of patients developing clinical extensive chronic GVHD and 45% of patients free of chronic GVHD (p = 0.0001). The incidence of recurrent leukemia was 28% in recipients developing both acute and chronic GVHD and 52% in patients free of both acute and chronic GVHD (p = 0.0001). These data confirm an apparent graft-versus-leukemia effect in patients developing GVHD after allogeneic marrow grafting. Current studies are aimed at determining the influence of such apparent adoptive immunotherapy within the different categories of leukemia and methods to manipulate and augment the clinical benefit of this observation.