The present study assessed the subjective and cardiovascular effects of intravenous nicotine in smokers and nonsmokers. Nonsmokers (n = 5) and smokers (n = 5) were administered a single dose of nicotine (0.75 or 1.5 mg) or saline on each of 3 days. The nicotine doses were given in ascending order in a double-blind fashion. Although smokers and nonsmokers manifested significant increases in systolic and diastolic blood pressure and heart rate 1 min after administration of all active test doses, the difference between peak heart rate and that measured at later times was greater in nonsmokers than in smokers. Nonsmokers and smokers also differed in subjective self-reports. In response to items on visual analogue scales indicative of positive effects (e.g., "good effects," "like drug," "use again," and "feel energetic"), smokers but not nonsmokers reported high scores (> 40) after nicotine injection. In addition, responses on the MBG and LSD subscales of the Addiction Research Center Inventory indicated that smokers experienced positive subjective effects after the test doses, whereas nonsmokers experienced disorientation. The fact that intravenous nicotine was not associated with positive subjective effects in nonsmokers indicates that repeated exposure is required to establish positive reinforcing effects of nicotine.