Previous work suggests that young women who smoke cigarettes regularly, or did so in the past, manifest a neurocognitive profile that is characterized by small but significant impairments of response inhibition and attention. The present study sought to determine whether variation in nicotinic cholinergic receptor (nAchR) genes impacts upon cognitive function in these domains by overall or differential effects on the performance of current, former and non-smokers. The study sample consisted of 100 female college students, current or past smokers, and 144 who had never smoked. All performed a computerized neurocognitive test battery and were genotyped for 39 single nucleotide polymorphisms in 11 nAchR genes. The results, derived from linear or logistic regression, show significant direct and interactive relationships between single nucleotide polymorphisms and haplotypes in several nAchR genes and performance on the Matching Familiar Figures Test (MFFT) Stroop test, Continuous Performance Task (CPT) and Tower of London (TOL) test. Response inhibition (MFFT, Stroop, CPT Loading Phase, TOL) was associated with variants in CHRNA2, CHRNA4, CHRNA5, CHRNA7, CHRNA9, CHRNA10, CHRNB2 and CHRNB3. Selective attention (Stroop) was associated with CHRNA4, CHRNA5, CHRNA9 and CHRNB2. Sustained attention (CPT Boring Phase) was associated with CHRNA4, CHRNA5, CHRNA7, CHRNA10 and CHRNB3. Up to 37% of the variance among the smokers and up to 47% of the variance among the non-smokers on the test measures was explained. Differences between smokers and non-smokers in neurocognitive function, putatively implicated in susceptibility to nicotine dependence, may be modulated by variants in nAchR genes, with potential implications for prevention and treatment.Keywords: Attention, cognition, nicotine, nicotinic cholinergic receptor genes, response inhibition, smoking Cigarette smoking is a complex behavior that is influenced by genetic, psychological and environmental factors (Den Exter Blokland et al. 2004;Li et al. 2003;Pomerleau et al. 1992). Nicotine is the core addictive component of cigarette smoke and its reinforcing properties are well established (Jarvis 2004). The effects of nicotine on cognitive function have long been thought to play a role in smoking behavior and to influence nicotine dependence (ND). Nicotine may serve as a positive reinforcer by facilitating attention capabilities (Newhouse et al. 2004;Rezvani & Levin 2001). However, studies comparing the effect of nicotine on non-abstinent smokers and non-smokers show relatively minor effects on cognition as compared with studies of abstinent and nonabstinent smokers. This has led to the view that nicotine serves as a negative reinforcer, abolishing the aversive withdrawal symptoms that an abstinent smoker experiences, thereby contributing to ND (Heishman et al. 1994). Nevertheless, positive effects of nicotine on cognitive function may be stronger in specific subpopulations, such as individuals with attention-deficit hyperactivity disorder (ADHD) (Sacco et al. 2004), where ...