Anisakiasis as well as allergic and anaphylactoid reactions to Anisakis simplex antigens are recently identified clinical entities. They are relatively frequent in countries with habitual raw food consumption, often in the form of large amounts of fish and sea food products. In this communication the relationship between HLA class II alleles and the IgE-specific immune response to A. simplex allergen was studied in a defined population in Northern Spain. Individuals with immediate-type Anisakis hypersensitivity and healthy controls were examined for HLA-DRB1, DQB1 and DQA1 alleles by sequence-specific oligonucleotide probe typing. Analysis of the HLA data among patients revealed increased phenotypic frequencies for DRB1*1502 and DRB1*0404 compared to healthy controls (p < 1 x 10(-7) and < 0.01, respectively). Analysis of haplotypic frequencies showed that the DRB1*1502-DQB1*0601 haplotype is significantly higher in patients with Anisakis hypersensitivity in comparison with the control population from the same region (p < 4 x 10(-8)). The data suggest that this haplotype can be considered to be a susceptibility factor for hypersensitivity to A. simplex antigens.