Inherited differences in the capacity of xenobiotic metabolizing enzymes might be an important factor in genetic susceptibility to cancer. Null genotypes of glutathione-S-transferases (GSTs) exhibit absence of enzymatic activity and are hypothesized to be at increased risk of developing cancers. The aim of the study was to examine whether null genotypes of GSTM1 and GSTT1 confer susceptibility to chronic myeloid leukemia (CML). We carried a case control study involving 80 consecutive North Indian CML patients (58 males, 22 females; age (mean+/-S.D.) 36.2+/-10.9 years) and 105 healthy individuals (59 males, 46 females; age (mean+/-S.D.) 36.8+/-11.3 years). Multiplex PCR was carried out to determine the frequency of GSTM1 and GSTT1 null genotypes. The relationship between GSTM1, GSTT1 genotypes and risk of CML was assessed by means of odds ratio (OR) with 95% confidence limits calculated by logistic regression. A test for trend (P(trend)) in increasing the risk of CML having more than one putative high-risk allele or genotype was evaluated by means of the chi-square test. There was no difference in the frequencies of the GSTM1 null genotype and the combined GSTM1 and GSTT1 null genotypes between patients and controls in the study. However, statistical significance was found with GSTT1 null genotype frequency in CML patients as compared to controls (16/80 (20%) versus 9/105 (8.5%); OR=2.67, 95% CI: 1.03-7.01). It projects a 2.67-fold increased risk for CML in individuals with GSTT1 null genotype as compared to those possessing both alleles of the gene. Our findings suggest that heritable GST status may influence the risk of developing CML.