This study examined the subjective and cardiovascular effects of two of the components of cigarette smoking when given separately: nicotine and airway sensations. Using a within-subjects design, six healthy volunteer smokers, age 18-45 years, who smoked at least 20 cigarettes per day were given six conditions in a randomized, counterbalanced order. The effects of IV nicotine, IV saline, and denicotinized cigarettes were compared to a standard 1-mg cigarette. The standard cigarette produced more of a calming effect and more irritability reduction than either the nicotine or airway sensations alone. The denicotinized cigarette was similar to the standard cigarette condition, except the cigarette condition was associated with higher feelings of "exhilaration." Many of the positive subjective effects from a denicotinized cigarette were comparable to that of a standard cigarette. These data support the hypothesis that replacement of the sensory cues of smoking with "airway sensory replacement" may be useful for smoking cessation.