Although nicotine dependence is one of the primary reasons why smokers cannot quit smoking, nicotine cannot explain all of the psychopharmacological effects of tobacco smoke. Accumulating evidence points to potent inhibition of monoamine oxidase (MAO) which metabolizes neurotransmitters relating to additive behaviour. We have therefore investigated the association between smoking behaviour and MAO ( variable number of tandem repeat in the promoter region and A644G) polymorphisms. The genotypes were examined in 504 Japanese outpatients (217 men and 287 women) who visited Aichi Cancer Centre Hospital. The age-adjusted odds ratios (aORs) were estimated by a logistic model. Among males, we did not find a significant association of the smoking habit with either of the polymorphisms. The median Fargastrom test for nicotine dependence (FTND) score among male current smokers was significantly higher with than without the 4-repeat allele (5.8 and 4.7, respectively). The aOR of FTND 6 versus FTND 6 was 2.72 (95% confidence interval 1.13-6.50) for males with the 4-repeat allele. Among females, the aOR of being current smokers compared to never smokers was 0.49 (0.26-0.93) for individuals with the 4-repeat allele. Our results indicate that the polymorphisms of influence the smoking habit for female, as well as the nicotine dependence and smoking initiation for male smokers. These findings among male smokers support the view that MAO affects a smokers' requirement for nicotine and may explain why some people are predisposed to tobacco addiction and why some individuals find it difficult to stop smoking.