en Original Article Original Article - Background: For screening sequence variations in genes, rapid turnover time is of fundamental importance. While, many of the current methods are unfortunately time consuming and technically difficult to implement. Denaturing high-performance liquid chromatography (DHPLC) method had been shown to be a high-throughput, time saving, and economical tool for mutation screening. Objective: In the present study DHPLC method was used to explore the potential association between estrogen receptor ? gene (ESR2) variants and male infertility. Materials and Methods: DNA from 96 men with infertility and 96 normal male as control were screened for mutation in the nine exons of the ESR2 gene, using WAVE� DHPLC device equipped with a DNA separation column and automated sequence analysis on the ABI Prism 310. Results: DHPLC evaluation of ESR2 gene in 96 infertile patients, revealed one heterozygous sequence variation (IVS 8�4G>A) near the 5� splicing region of intron 8 in 5 patients. No variation was identified in control population. Conclusion: Mutation detection by DHPLC, as it is presented in this context, is a high-throughput, quick, and economical tool for mutation screening. The gene alterations in ESR2 gene that we�ve found might increase susceptibility to infertility; but without cDNA screening, the consequences of these genetic alterations cannot be predicted DHPLC, Male infertility, ESR2 gene, Mutation 9 13 http://ijrm.ir/browse.php?a_code=A-10-100-43&slc_lang=en&sid=1 Mir Davood Omrani Yes Agneta Nordenskhold No