Glutathione S-transferase (GST) plays a major role in the detoxification of many compounds by conjugation with glutathione. GSTM1 and T1, which are important members of the GST multigene family, are polymorphic in humans. Complete deletion of the gene results in the null genotype and loss of function. However, it is not clear whether deletion of this gene is associated with a vulnerability to methamphetamine (MAP) abuse. To clarify the potential role and mechanisms of genetic polymorphisms of GSTM1 and T1 in susceptibility to MAP abuse in the Japanese population, we investigated GSTM1 and T1 polymorphisms in subjects with diagnosed MAP-related disorders and in control groups. The risk of MAP abuse associated with GSTM1 null genotype was significantly higher only in females than in subjects with the GSTM1 genotype. GSTM1 and GSTT1 null genotype combined conferred increased risk for MAP abuse compared with GSTM1 and GSTT1 genotype combined. In conclusion, we found that GSTM1 gene deletion may contribute to a vulnerability to MAP abuse in female subjects. Moreover, we identified an association between GSTM1 and GSTT1 null genotype combined and risk of MAP abuse in the Japanese population.