Summary. The association between various human leucocyte antigen (HLA) alleles and the occurrence of acute and chronic graft‐versus‐host disease (GVHD) was evaluated in 493 haematopoietic stem‐cell transplant (HSCT) patients with HLA identical sibling donors. There were 307 men and 186 women with a median age of 30 years (0·2–77). Most of the patients had a haematological malignancy and received total body irradiation or busulphan combined with cyclophosphamide as conditioning before transplantation. GVHD prophylaxis consisted of monotherapy with methotrexate (MTX) or cyclosporin (CsA) in 118 patients, MTX + CsA in 323, T‐cell depletion in 28 and other combinations in 24. In total, 84 patients (17%) received a peripheral blood stem‐cell graft, whereas the rest received bone marrow. The cumulative incidence of acute GVHD grades II–IV was 20%, and chronic GVHD 46%. In the multivariate analysis, HLA‐A10 (OR 2·14, CI 1·04–4·41, P = 0·03) and HLA‐B7 (OR 1·80, CI 1·04–3·12, P = 0·03) correlated with an increased risk of acute GVHD grades II‐IV. We also found an association between HLA‐B27 (RR 0·60, CI 0·37–0·95, P = 0·04) and a lower incidence of chronic GVHD. These HLA alleles were independent of other known risk factors for acute or chronic GVHD, as shown by multivariate analysis. These results show that major histocompatibility comlex (MHC) alleles may influence the incidence of GVHD in HSCT with HLA identical sibling donors.