To investigate whether the equine major histocompatibility complex (MHC) gene region influences the production of mould-specific immunoglobulin E antibodies (IgE), alleles of the equine leukocyte antigen (ELA-A) locus and three microsatellite markers (UM-011, HTG-05 and HMS-42) located on the same chromosome as the equine MHC were determined in 448 Lipizzan horses. Statistical analyses based on composite models, showed significant associations of the ELA-A and UM-011 loci with IgE titres against the recombinant Aspergillus fumigatus 7 antigen (rAsp f 7). UM-011 was also significantly associated with IgE titres against the recombinant Aspergillus fumigatus 8 antigen (rAsp f 8). In addition to the loci mentioned above, the MHC class II DQA and DRA loci were determined in 76 Lipizzans from one stud. For IgE levels against rAsp f 7, the composite model showed the strongest association for DQA ([Formula: see text]P) while for rAsp f 8 specific IgE levels, similarly to the results found with all 448 horses, the strongest association was found with UM-011 (P=0.01), which is closely linked with the MHC class II DRB locus. These results suggest that the equine MHC gene region and possibly MHC class II loci, influence the specific IgE response in the horse. However, although the strongest associations were found with DQA and UM-011, this study did not distinguish if the observed effects were due to the MHC itself or to other tightly linked genes.