Background. We examined whether there are genetic influences on nicotine withdrawal, and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Method. Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from young adult Australian twins reporting any cigarette use (3026 women, 2553 men; mean age 30 years). Results. Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%), and similar in men and women. The exceptions were depressed mood upon withdrawal, which had stronger additive genetic influences in men (53%) compared to women (29%), and decreased heart rate, which had low heritability (9%). Although prevalence rates were substantially lower for DSM-IV nicotine withdrawal syndrome (15·9%), which requires impairment, than for the DSM-IV nicotine dependence withdrawal criterion (43·6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ('progression'), quantity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/ dependence (genetic correlations=0·53-0·76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Conclusions. Our results suggest that at least some individuals become 'hooked' or progress in the smoking habit, in part, because of a vulnerability to nicotine withdrawal.