To evaluate the association between genetic polymorphism of GSTM1, GSTT1 and development of bladder cancer, a hospital-based case-control study was conducted in South Korea. The study population consisted of 232 histologically confirmed male bladder cancer cases and 165 male controls enrolled from urology departments with no previous history of cancer or systemic diseases in Seoul during 1997-1999. The GSTM1 null genotype was significantly associated with bladder cancer (OR: 1.6, 95% CI: 1.0-2.4), whereas the association observed for GSTT1 null genotype did not reach statistical significance (OR: 1.3, 95% CI: 0.9-2.0). There was a statistically significant multiple interaction between GSTM1 and GSTT1 genotype for risk of bladder cancer (P=0.04); the risk associated with the concurrent lack of both of the genes (OR: 2.2, 95% CI: 1.2-4.3) was greater than the product of risk in men with GSTM1 null/GSTT1 present (OR: 1.3, 95% CI: 0.7-2.5) or GSTM1 present/GSTT1 null (OR: 1.1, 95% CI: 0.6-2.2) genotype combinations.