Nicotine replacement is a promising new approach to aid smoking cessation, and various methods of delivery are being developed. One new device is a smoke-free cigarette (Favor) that has been test-marketed in several US states. Without lighting up, it delivers nicotine vapor and is free of other harmful products of tobacco smoke. To examine its therapeutic potential, we measured plasma nicotine concentrations before, during, and after its use in eight male subjects. Very little nicotine was absorbed when it was puffed like a conventional cigarette. However, with an intensive schedule of puffing at four further smoke-free cigarettes over a 20-minute period, plasma nicotine concentrations were increased by an average of 17.3 ng/mL (107.3 nmol/L) (range, 10.9 to 30.4 ng/mL [67.6 to 188.5 nmol/L]). Heart rate and blood pressure also increased significantly. The rate of nicotine absorption was slow and resembled that obtained from nicotine chewing gum, suggesting that most of the nicotine was deposited in the mouth, throat, and large airways and did not reach the lung alveoli. Despite the slow absorption, the plasma nicotine levels produced could be of therapeutic value as an aid to smoking cessation.