Glutathione S-transferase (GST) isoenzymes are involved in the detoxification of major carcinogens present in tobacco smoke. It is thus conceivable that deficiency in GST activity due to homozygous deletions of the GSTM1 and GSTT1 genes (the null genotypes) may modulate susceptibility to smoking-induced cancers. The influence of the GSTM1 and GSTT1 null genotypes on larynx cancer risk among the Korean population were evaluated using peripheral blood DNA from 82 larynx cancer patients and 63 healthy controls, all of whom were male current smokers. Increased larynx cancer risk was related to the GSTM1 null genotype (odds ratio (OR)=3.53, 95% confidence interval (CI)=1.27-9.83). The OR associated with the GSTT1 null genotype was also increased, but did not reach statistical significance (OR=1.83, 95% CI=0.70-4.79). Individuals lacking both the GSTM1 and GSTT1 genes were at a significantly higher risk for larynx cancer than individuals with both genes present (OR=4.04, 95% CI=1.33-12.30). These data confirm that the GSTM1 null genotype is an important risk modifier for larynx cancer among Korean smokers and combined GSTM1 and GSTT1 null genotypes could be a useful predictor of genetic susceptibility to larynx cancer.