Fifty-seven atopic, skin-test positive, unrelated Italian patients with allergic rhinitis or rhinoconjuntivitis, sensitized to a single allergen, were studied. Nine of them showed hypersensitization to grass pollen, thirty-eight were allergic to Urticaceae, nine had positive skin reactivity to mites and one to Betula verrucosa. To investigate the immunogenetic components of disease susceptibility, restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, DQ alpha and DO beta genes, and RFLP analysis of switch regions of the immunoglobulin heavy chain constant genes were carried out. Gene frequencies of the alleles at these loci were not different between patients and Italian controls. Subdividing the patients according to allergen reactivity or to the presence of asthma, HLA frequencies did not show any differences, whereas the 3.8 Kb fragment at the switch gamma 4 locus was significantly more frequent in patients with allergy to Urticaceae than in the control population (p = .0087; P-c < .05). Moreover, an increased frequency of the 4.1 Kb fragment at the same locus was noted in patients with asthma compared to controls (p = .0002; P-c < .01). These results support: the hypothesis of a multifactorial inheritance of allergy, the Ig heavy chain constant gene region being one of the loci contributing to susceptibility (Fund. Clin. Immunol. 4: 35-44, 1996).