To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.