We analyzed the treatment of acute GVHD following allogeneic, related or unrelated donor bone marrow transplantation (BMT). Of 510 patients transplanted between January 1986 and July 1991, 272 (53.0%) developed acute GVHD. Patients (n = 240) received treatment with either corticosteroids (n = 209), antithymocyte globulin (ATG)/prednisone (n = 26), or an anti-T cell immunotoxin (n = 5). After 28 days, 33% (79/240) had achieved a response to primary therapy; 24% a complete response. Ninety-five patients received 1 or more courses of salvage immunotherapy and 26 (27%) responded. In multivariate analysis, a response to primary therapy was the single most important factor independently predicting a lower risk of subsequent chronic GVHD (P < .0001) and improved long-term survival (P = .01). The GVHD clinical stage score, which we previously described, had significant predictive value for response to therapy and freedom from chronic GVHD. The conventional clinical grade had no such predictive value. In multivariate analysis, transplantation from a mismatched or an unrelated donor was not of independent importance in predicting either acute GVHD treatment response or chronic GVHD. However, these alternative donor transplants led to poorer survival. This analysis identifies patient subsets having GVHD with a low likelihood of response to conventional immunosuppressive treatment and may be used to indicate those needing early application of more intensive therapy. More important, however, the overall low response rates observed suggest that more effective treatment for acute GVHD is still required to improve the results of transplantation therapy.