Summary.  Acquired haemophilia (AH) is a rare autoimmune bleeding disorder, which arises as a result of the spontaneous production of autoantibodies against endogenous factor VIII. The breakdown in immune tolerance is thought to be a result of a combination of genetic and environmental factors. Both human leucocyte antigen (HLA) and cytotoxic T lymphocyte antigen 4 (CTLA‐4) play an important role in the maintenance of peripheral T‐cell tolerance. A higher frequency of HLA class II alleles and single nucleotide polymorphisms of the CTLA‐4 gene have been observed in some autoimmune diseases and severe haemophilia A. In 57 patients with AH, significantly higher frequencies of the HLA class II alleles DRB*16 [odds ratio (OR) 10.2] and DQB1*0502 (OR 2.5) have been detected when compared with controls. The CTLA‐4 + 49 G allele has also presented with a significantly higher frequency in the same cohort of patients with AH (OR 2.17). This observation was mainly because of a higher frequency of the CTLA‐4 + 49 G allele in female patients. These findings suggest that immune response genes may contribute to the development of anti‐factor VIII autoantibodies in AH.