Regardless of actual nicotine content, expectations about the nicotine content of a cigarette influence the rewarding subjective effects of smoking, and may even affect cognitive performance. These effects are theorized to be mediated by beliefs about effects of cigarette smoking, or response expectancies. However, few studies have directly manipulated response expectancies. Understanding the effects of such manipulations could improve effectiveness of nicotine-dependence treatments and medications. Using a 2 × 2 between-subjects factorial design, cigarette smokers (N = 80) smoked either a nicotine or a placebo (denicotinized) cigarette crossed with instructions that the cigarette would either enhance or impair cognitive and motor performance. As predicted, participants in the "told enhance" condition reported significantly greater beliefs that nicotine had beneficial effects on performance than those in the "told impair" condition. Compared to those "told impair," those "told enhance" reported more psychological reward, enjoyable physical sensations, and craving reduction from the cigarette, as well as greater motivation to perform well on a cognitive task. Relative to placebo cigarettes, nicotine cigarettes produced greater reports of satisfaction, craving reduction, and dizziness. Smoking a nicotine cigarette produced better performance on the Rapid Visual Information Processing Task, a test of sustained attention; but the expectancy manipulation had no effect. These data suggest that response expectancies can be experimentally manipulated and can influence perceived rewarding effects of cigarette smoking, but do not appear to affect cognitive performance. These findings add to our understanding of the benefits and limitations of expectancy manipulations, both experimentally and as a treatment technique.