OBJECTIVES: (i) To examine the role of apoptosis in the pathogenesis of DNA damage in semen from infertile men. (ii) To assess the effects of smoking on apoptotic markers and seminal parameters among infertile men. (iii) To assess the correlation of apoptosis with conventional semen parameters. MATERIALS AND METHODS: The study was carried out on 70 men with idiopathic infertility, divided into two groups: thirty infertile non smokers and forty infertile smokers. In addition to 60 fertile men (30 non smokers and 30 smokers) as control group. Each subject provided semen for analysis of parameters, determination of % of DNA fragmentation, s-Fas, caspase-3 activity levels and cotinine levels. RESULTS: The results revealed that infertile men, particularly smokers have significantly lower semen variables and significantly higher levels of apoptotic variables (% of DNA fragmentation, s-Fas and caspase-3 activity) in addition to cotinine. CONCLUSIONS: The present findings provide additional evidence supporting the importance of the evaluation of apoptotic markers to test male infertility particularly among smokers.