We have studied the relationship between HLA class II haplotypes and alleles, and the IgE antibody response to a highly purified allergen, Ole e I, in allergic patients. Ole e I, is the major antigen from the pollen of olive tree that grows mainly in the Mediterranean. Genomic DNA typing was performed in 40 unrelated patients with seasonal allergic pollenosis who had specific IgE antibodies against Ole e I, detected by double-antibody radioimmunoassay. HLA-DRB and -DQB loci were analyzed by PCR-SSO and RFLP. Phenotypic frequencies were compared with those of 179 healthy unrelated individuals. Significant increases in the phenotypic frequencies of DR7 (pf = 67.5% vs 31.3% in the control population, pc = 0.0023) and DQ2 (pf = 90.0% vs 48.0%, pc = 0.0003) were found, indicating an association between DRB1*0701/2, DQB1*0201 alleles and the IgE antibody response to Ole e I. This is the first time that the HLA-DQ gene has been associated with a positive allergic response.