Bovine neonatal pancytopenia (BNP), a disease of neonatal calves, has been described in a number of European countries from 2006. The disease is characterised by haemorrhagic diathesis caused by profound thrombocytopenia and bone marrow depletion resulting in high mortality within three weeks of birth. A number of hypotheses including a novel virus infection, plant toxins, a vaccine induced autoimmune disease, or a genetic defect have been suggested to explain the aetiology of this disease. However, as the numbers of cases in affected herds remains small, it is hypothesised that the genetic background of the calf may influence disease susceptibility. To test this we focused on the major histocompatibility complex (MHC) which is often associated with variations in immune response and susceptibility to autoimmune and infectious diseases. Forty three cases of BNP and sixty eight controls from Holstein dairy cattle were genotyped at the polymorphic class II MHC DRB3 locus. Twenty DRB3 alleles were identified with seven alleles appearing at frequencies ≥ 0.05. A comparison of the allelic frequencies between diseased and control groups showed that there was no evidence for any significant differences (adjusted p value ranging from 0.66 to 1), suggesting that the MHC does not appear to be a predisposing risk factor in the development of BNP in Holstein dairy cattle.