Infertility/subfertility affects approximately 5-7% of the male population worldwide and may increase in the future [1]. Infertility/subfertility of undefined cause is referred to as idiopathic infertility/ subfertility, but is likely to be of genetic origin. Although the number of candidate spermatogenesis genes is steadily increasing, their patho genic role is largely unknown. A recent report focused on gene polymorphisms as a cause for impairment of sperm production and male infertility [2]. The mitochondrial DNA polymerase gamma (POLG) gene is located on chromosome 15q24 and contains a poly morphic CAG repeat [3]. The common allele contains 10 CAG repeats and occurs at a uniformly high frequency (88-96%) in Eurasian populations [4-6]. The not10 CAG repeat alleles (ranging from six to 15) are considered as mutants. Rovio et al. [3] reported a strong association between the absence of the 10 CAG allele and male infer tility, specifically with moderate oligozoospermia, and hypothesized that the presence of two mutant alleles would lead to a suboptimal polymerase activity with accumula tion of mutations in mtDNA, impaired energy metabolism in the spermatogenic cells and disturbance of sperm pro duction and/or differentiation. Later Jensen et al. [7] sug gested that the POLG gene polymorphism should be con sidered as a possible contributing factor in patients with unexplained subfertility and normal semen parameters. However, studies in Italy [8,9] and France [10] did not confirm any influence of the POLG CAG polymorphism on the efficiency of spermatogenesis and male fertility. Recently, a difference has been reported in the number of CAG repeats of the POLG gene between Chinese and European males, and it was proposed that the 10/not 10 CAG genotype may affect sperm motility n Chinese males [11]. The aim of this study was to assess whether different POLG CAG alleles are associated with impaired spermato genesis and infertility/subfertility in Macedonian men.