Background: Transporter antigen peptide 1 (TAP1) and TAP2 gene products form a transporter molecule involved in antigen presentation. Polymorphic residues have been described in both genes and could have functional consequences in the immune response. Objective: We designed a case-control study to investigate the potential association of polymorphism of the TAP1 gene with atopy. Methods: We used the amplification refractory mutation system polymerase chain reaction to characterize TAP1 gene polymorphism in 84 unrelated Tunisian patients with atopy and 81 healthy control subjects. Results: Analysis of TAP1 polymorphism in Tunisian patients with atopy and in unaffected control subjects demonstrates a high relative risk (RR) of atopy in carriers of a codon (d) corresponding to a glycine at position 637 of the TAP1-B and TAP1-D alleles. The relative risk of allergic asthma is markedly higher in homozygotes (d/d) (RR = 22; p ≤ 0.0001). The TAP1-D allele, not observed in European populations, has a frequency of 5% in the Tunisian control subject group. A major increase of the frequency (f) of the D allele is observed in patients with allergic asthma (f = 35%) and in those with allergic rhinitis (f = 22%), indicating a high relative risk of allergic asthma (RR = 10.2; p ≤ 0.0001) and of allergic rhinitis (RR = 5.4; pH 0.005) in individuals carrying this allele. DD homozygotes were found only among patients with allergic asthma (23% of patients with asthma). Further evidence of the strong association between TAP1 polymorphism and atopy was provided by the finding that atopy is transmitted by inheritance of the glycine-637 marker. Conclusions: Tunisian persons carrying the glycine-637 of the TAP1 protein may have an increased risk of atopy. Specific association was found between the homozygous TAP1 D/D genotype and allergic asthma. (J Allergy Clin Immunol 1997;99:216-23.)