Epidemiological documents show an association of tobacco smoking rates and perceived stress levels. This study, using an animal model of nicotine self-administration, investigated effects of stress on nicotine-taking behavior. Sprague-Dawley rats were trained to intravenously self-administer nicotine. Thirty minutes before test sessions, animals were challenged with an intraperitoneal administration of a pharmacological stressor yohimbine. In the low nicotine-taking rats, yohimbine challenge enhanced lever-press responses and thereby nicotine intake. In contrast, no such effect was observed in the high nicotine-taking rats. After yohimbine challenge, nicotine intake in those originally low nicotine-taking rats remained at the heightened level. These findings demonstrate that exposure to stress facilitates nicotine self-administration in the rats previously consuming less nicotine and makes them to become high nicotine-taking subjects. The results of this study suggest that stressful life events may be effective in increasing tobacco smoking in light to moderate smokers and therefore increase the prevalence of nicotine dependence. As such, reducing stress levels in daily life may prove to be an effective approach to the prevention of nicotine addiction.