In this study we investigated the relationship between HLA class II alleles and the IgE-specific immune response to the 4.7 kDa polypeptide hevein of Hevea brasiliensis, a major latex allergen, 51 individuals with immediate-type latex allergy and 90 controls were examined for the polymorphisms in exon 2 of HLA-DRB1, 3, 4, 5 and DQB1 by sequence-specific oligonucleotide probe typing. 35 (69%) out of 51 latex-sensitized subjects showed positive hevein-specific IgE values. Analysis of the HLA data among these 35 subjects revealed increased phenotype frequencies for DR4 (22/35, 63%) and DQ8 (18/35, 51%) when compared with those in the 16 hevein-negative but latex-positive subjects (DR4: 2/16, 13%, p = 0.0009, Pc = 0.047; DQ8: 0/16, p = 0.0003, pc = 0.018) and with healthy controls (DR4: 22/90, 24%, p = 0.00012, pc = 0.013; DQ8: 16/89, 18%, p = 0.0003, pc = 0.036). Finally the DR4-DQ8 haplotype frequency was significantly elevated in hevein-positives when compared with hevein-negatives (51% vs. 0, p = 0.0003, pc = 0.034) or controls (51% vs. 18%, p = 0.0002, pc = 0.045) The present data suggest DR4 and DQ8 to be operating jointly as susceptibility factor for the allergy to hevein.