The role of the polymorphic glutathione S-transferase genes GSTM1 and GSTT1 in the development and in the clinicopathological outcome of bladder cancer was investigated in 37 Egyptian bladder cancer patients and 34 matched controls. Of the 37 patients studied, 26 had transitional cell carcinoma (TCC) and 11 had squamous cell carcinoma (SCC). Fourteen out of twenty-six TCC and four out of eleven SCC patients were infected with schistosoma. We observed an increased relative risk for bladder cancer associated with the GSTM1 null genotype (OR = 2.99; 95% CL = 1.01-9.00; p = 0.02). The relative risk was more pronounced in squamous cell carcinoma (SCC) (OR = 5.70; 95% CL = 0.91-36.70; p = 0.03) than in transitional cell carcinoma (TCC) (OR = 2.39; 95% CL = 0.73-7.90; p = 0.08). Our results also indicate that the GSTT1 polymorphism is individually associated with increased risk for bladder cancer (OR = 4.93; 95% CL = 1.39-18.42; p = 0.004) with no preferential increase in risk with respect to the type of the carcinoma. Individuals with the null genotype for both GSTM1 and GSTT1 were at a significantly higher risk for developing bladder cancer than individuals with both genes present (OR = 9.92; 95% CL = 1.84-46.90; p = 0.001). These individuals were more susceptible to developing SCC than TCC (OR = 14.16; 95% CL = 1.35-131.35; p = 0.01; and OR = 8.5; 95% CL = 1.38-60.10; p = 0.007, respectively). In conclusion, our results indicate that the null genotypes for GSTM1 and GSTT1, either individually or in combination, are important host risk factors for bladder cancer. In addition, the null GSTM1 genotype may also affect the clinicopathological tumor outcome. Since the deleted genotypes for GSTM1 and GSTT1 are prevalent in the general population, the identification of these individuals may provide a useful public health approach for early detection and prevention of environmental cancers.