The present study aims to evaluate oxidative DNA damage in human sperm and the association with cigarette smoking. The level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA, cotinine concentration in seminal plasma, and conventional seminal parameters such as semen volume, sperm density, viability, motility, and normal morphology were determined in 60 healthy subjects. It was found that the sperm DNA of smokers contained a significantly higher amount of 8-OHdG than that of nonsmokers (6.19 +/- 1.71 vs. 3.93 +/- 1.33 8-OHdG/10(5) dG, P < 0.001). The level of 8-OHdG in sperm DNA was also closely correlated to seminal cotinine concentration (r = 0.38, P < 0.05). These findings suggest that cigarette smoking enhances the extent of DNA damage in sperm. In contrast, no significant difference was observed for conventional parameters between smokers and nonsmokers, suggesting that the level of 8-OHdG in sperm may reflect the deleterious effect of cigarette smoking on sperm quality more accurately than conventional seminal parameters. Further investigation is required to understand the exact biologic and pathologic significance of oxidative damage to sperm DNA and the possibility of using 8-OHdG for the assessment of sperm quality.