RATIONALE: Nicotine and non-nicotine components of cigarette smoke contribute to its reinforcing effects; however, the specific role of each component in maintaining behavior has not yet been elucidated. OBJECTIVES: To assess the reinforcing effects of nicotine and non-nicotine components of cigarette smoke by presenting a concurrent choice paradigm in which participants had access to intravenous (IV) nicotine infusions vs. saline (placebo) infusions and puffs from denicotinized ("denic") cigarettes vs. air (sham puffs). We also measured the effects on self-administration of prior satiation with each component. METHODS: Sixteen smokers participated in seven sessions: 1) a baseline smoking assessment, used to tailor the nicotine dose per infusion; 2) two sessions for training discrimination of IV nicotine vs. saline infusions and denic smoke vs. sham puffs; and 3) four sessions assessing choice behavior after different satiation conditions. RESULTS: Denic smoke was self-administered more than any other alternative, including IV nicotine. IV nicotine, however, was preferred over IV saline and sham puffs. Preference for denic smoke vs. IV nicotine was inversely correlated with subjective ratings of "comfort" associated with nicotine. Smoke satiation reduced the number of denic puffs taken during choice periods, while prior nicotine administration did not affect puffing behavior. Smoking withdrawal symptoms were alleviated both by nicotine administration and by denic smoke. CONCLUSIONS: In established smokers, non-nicotine aspects of cigarette smoking have potent reinforcing effects. While current smoking cessation pharmacotherapies primarily address the nicotine component of cigarette addiction, future cessation strategies should also be designed to target non-nicotine factors.