As a help of the mechanism elucidation of nicotine dependence, we studied the relationship between glycogen synthase kinase (GSK) - 3beta -1727A/T and -50T/C genetic polymorphisms, which are reported to be related to bipolar disorder. We genotyped the two polymorphisms in the GSK-3beta gene using a polymerase chain reaction (PCR) in 103 healthy controls (never smokers) and 71 smokers with FTND scores of 3 or above. There is no significant relationship between the polymorphism of GSK-3beta -1727A/T and the nicotine addicts. However, it was shown that GSK-3beta -50T/C polymorphism was significantly associated with the nicotine dependence. There was significantly lower T-allele frequency in the smokers than controls (chi2 (2) = 23.42, P = 0.01; chi2 (1) = 12.17, P = 0.01).