In this study, the authors evaluated the combined impact of smoking and stress on catecholaminergic and cardiovascular reactivity in disease-free adult smokers. Smokers participated in 2 laboratory sessions, including a baseline and a mental-stressor phase (reaction time and mental math), once while smoking-deprived overnight and once while nondeprived. Nonsmoking controls also participated in an identical laboratory session, without the smoking manipulation. The authors obtained cardiovascular measures during each phase and measured catecholamine levels immediately after each phase. For nondeprived smokers, measures of norepinephrine, epinephrine, heart rate, and systolic blood pressure (SBP) were larger for the mental-stressor phase than for the baseline phase. The authors found no such increases for deprived smokers, and only SBP increased for controls from the baseline phase to the mental-stressor phase. The results suggest that ad lib smoking increases catecholamine and cardiovascular response to stress in smokers.