Cigarette smoking decreases life expectancy, causes devastating health complications, and costs society billions of dollars each year. These untoward consequences are especially pronounced among persons with schizophrenia (SCZ) because approximately 80% to 95% of this group smokes cigarettes. These high prevalence rates underscore the need for research investigating the determinants of smoking in patients with SCZ. Several researchers have observed that nicotine improves specific symptoms of SCZ including negative symptoms, negative affect, and cognitive deficits. This has led to the hypothesis that patients with SCZ smoke in an attempt to self-medicate. However, the mechanism(s) by which nicotine has its positive effect on symptoms remains unclear. The current proposal posits that neural inhibition (NI) is a physiological mechanism of this effect, while variation in the alpha-7-nicotinic receptor subunit gene (CHRNA7) represents the genetic underpinnings of these processes. The proposed study will assess NI and symptom improvement after acute administration of nicotine to both smokers and nonsmokers with SCZ. In addition, NI and CHRNA7 variation will be tested as predictors of patients' ability to reduce/quit smoking following smoking treatment. These data may lead to the development of new pharmacological strategies for treating the symptoms of SCZ and new methods for assisting these patients to quit smoking.