Effects of smoking on spontaneous bilateral skin conductance were studied as a consequence of interactions with set and setting. Bilateral skin conductance was recorded in six men and six women who smoked and an equal number of nonsmokers on two different days. On the first day, spontaneous electrodermal activity was recorded before and after a 10-minute rest period during which half the smokers smoked a cigarette. On the second day, one week later, spontaneous activity was again recorded before and after a 10-minute rest period during which the remaining smokers smoked a cigarette. Nonsmokers did not smoke at any time. Following smoking there was a significant negative correlation between a preference for visual over nonvisual imagery and spontaneous skin conductance responsivity in the left as compared to the right hand. Correlations were significantly different in smokers and nonsmokers. Smokers showed significantly greater preferences for either visual or nonvisual imagery than nonsmokers. Nonresponding nonsmokers were higher on the psychoticism (P) scale of the Eysenck Personality Questionnaire (EPQ) than responding nonsmokers. Smokers scored higher on P than nonsmokers. Interactions between personality, cognitive style, and the experimental situation, set, and setting were discussed in relation to the arousing effects of nicotine.