Background: Cigarette smoking, a major cardiovascular risk factor, has been shown to be associated with impaired endothelium- dependent vasodilation is probably affected by cigarette smoking. Cigarette smoke contains superoxide anions and a great number of other reactive oxygen species [ROS], the accumulation of which brings about oxidative damage of endothelial cells. A free radical catalyzed isomers of arachidonic acid [8-epi- PGF_2∞] is a potent vasoconstrictor and serves as a marker of oxidative stress. Objective: To evaluate the level of serum [NO] and urinary 8 epi- PGF_2∞ in mild, moderate, and heavy smokers and to correlate their levels with urinary cotinine which is considered a sensitive markers of exposure to nicotine of tobacco smoke. Subjects: 20 heavy smokers, 20 moderate smokers, 20 mild smokers, and 20 controls were the material of the present study. Results: The present study revealed significant increase in urinary 8 epi- PGF_2∞ in smokers compared to control subjects. Also significant increase was found in urinary 8 epi- PGF_2∞ in heavy compared with moderate smokers. However, there was a significant decrease in serum [NO] in the same two groups as compared to controls. Positive correlation for urinary 8 epi- PGF_2∞ and negative correlation for serum [NO] as compared to urinary cotinine were detected. It may be concluded that concentration of 8 epi- PGF_2∞ and cotinine in the urine as well as NO in the sera of smokers might give more accurate information about ROS which play an important role in the pathogenesis of many diseases affecting the physiological functions of body systems.