Background: Epidemiologic studies of drinking water disinfection byproducts have focused primarily on the carcinogenic potential of chlorination byproducts. Because drinking water has been ozonated in France for decades, we were able to assess the carcinogenic risk of the disinfection byproducts generated by both ozonation and chlorination. Methods: We used data from a case-control study of bladder cancer conducted between 1985 and 1987 in 7 French hospitals. We compared 281 cases and 272 controls for whom we could reconstruct at least 70% of the residential exposure to drinking water contaminants over a 30-year period. Results: When we took potential confounders and exposure to chlorination byproducts into account, the risk of bladder cancer decreased as duration of exposure to ozonated water increased (OR = 0.60 [95% CI = 0.3-1.3] for 1-9 years; OR = 0.31 [0.1-0.7] for 10 years or more). Simultaneously, the risk of bladder cancer increased with duration of exposure to chlorinated surface water and with the estimated trihalomethane content of the water. Our data suggest that ozonation reduces the risk associated with the chlorination of surface water and that ozonation alone could have an independent beneficial effect on bladder cancer risk. Conclusions: Our results are consistent with experimental evidence that ozonation in combination with chlorination decreases the concentration of trihalomethane in treated water and eliminates some of the mutagenicity of raw water.