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Aspirin-exacerbated respiratory disease (AERD) is nonatopic asthma, and the role of heat shock protein (HSP) 70 in AERD remains unknown. We analyzed HSP70 gene polymorphisms in Japanese patients with AERD.The single-nucleotide polymorphisms in HSPA1B-179C>T and 1267A>G gene were examined in patients with AERD and those with aspirin-tolerant asthma (ATA). All patients were in a stable condition.There were significant differences in total serum IgE levels, peripheral blood eosinophil count, and prevalence of atopy between AERD and ATA. The patients with AERD showed higher frequencies of the CT/TT genotype of the HSPA1B-179C>T than that of the CC genotype compared to ATA (P < 0.001). They showed higher frequencies of the GG genotype of the HSPA1B1267A>G than that of the GA/AA genotype compared to ATA (P < 0.001). These differences were irrespective of the sex for the genotypes analyzed. The frequency of HSPA1B-179C/1267A haplotype was significantly higher in AERD compared to ATA (P < 0.001; odds ratio, 3.154; 95% confidence interval, 1.916-5.193). Among the clinical and hematological characteristics investigated, AERD showed a significant variance in peripheral blood eosinophil count according to the association of the 2 HSP70 gene polymorphisms (P = 0.033), but not in ATA.Our findings first suggest that the association between HSPA1B-179C>T and 1267A>G gene sequence variations might be implicated in the development of AERD.