Chlorine is by far the most commonly used chemical for the disinfection of water supplies in North America. However, chlorine reacts with organic material in the raw water producing a number of halogenated hydrocarbon by-products. This population-based case-control study in Ontario, Canada examined the relationship between bladder cancer and exposure to chlorination by-products in public water supplies. Residence and water source histories and data from municipal water supplies were used to estimate individual exposure according to water source, chlorination status, and by-product levels (represented by trihalomethane [THM] concentration). Exposures were estimated for the 40-year period prior to the interview, using 696 cases diagnosed with bladder cancer between 1 September 1992 and 1 May 1994 and 1,545 controls with at least 30 years of exposure information. Odds ratios (OR) adjusted for potential confounders were used to estimate relative risk. Those exposed to chlorinated surface water for 35 or more years had an increased risk of bladder cancer compared with those exposed for less than 10 years (OR = 1.41, 95 percent confidence interval [CI] = 1.10-1.81). Those exposed to an estimated THM level > or = 50 micrograms/liter for 35 or more years had 1.63 times the risk of those exposed for less than 10 years (CI = 1.08-2.46). These results indicate that the risk of bladder cancer increases with both duration and concentration of exposure to chlorination by-products, with population attributable risks of about 14 to 16 percent. Chlorination by-products represent a potentially important risk factor for bladder cancer.