The proposed study will examine the threshold for nicotine self-administration using four different nicotine doses in male and female smokers with or without nicotine dependence (light and intermittent smokers). The investigators propose a double-blind, placebo-controlled study that will enroll 150 individuals with 32 male and 32 female smokers with a total of 64 completers, (16 of each group will be dependent and 16 will be non-dependent). Smokers will participate in four sessions: four test sessions. In each of the four test sessions, smokers will be randomly assigned to one of the four doses of nicotine (1.5, 3.0, 4.5, and 6.0 mcg/kg, or about 0.1, 0.2, 0.3, and 0.4 mg/70 kg). At the beginning of each test session, smokers will sample the assigned nicotine dose and placebo (saline) and then have the opportunity to choose between nicotine and placebo for a total of five choices over a 90-minute period. The main outcomes will be threshold dose (the minimum dose of nicotine that is self-administered more than placebo) and the slope of dose-response for nicotine self-administration (changes in nicotine self-administration per unit change in nicotine dose).