The chlorination of river water in purification plants is known to produce carcinogens and genotoxins. The Yodo River system was studied in regard to the trihalomethane formation potential (THMFP) and mutagen formation potential (MFP) by the chlorination of river water and the discharge of sewage effluent. Overall, both THMFP and MFP are higher in the downstream region of the Yodo River system than in the upstream Uji and Katsura River region, whereas the formation potentials are high in the upstream part of the Kizu River. Detailed surveys were carried out on the Nabari River and other tributaries to the Kizu River. It was revealed that the Nabari and the upper Kizu rivers contribute 49.9% and 41.9% of the THMFP and 47.9% and 44.7% of the MFP pollution load to the main stream of the Kizu River, respectively. The contribution rates of the upper Kizu River could be attributed to three rivers, the uppermost Kizu, Hattori, and Kume rivers, and household sewage waterways at 10.6%, 17.3%, 10.9%, and 3.1% for THMFP and at 9.5%, 17.3%, 12.5%, and 5.5% for MFP, respectively. The main cause of water pollution in the upper reaches of the Kizu River may be attributable to both sewage effluent discharged directly into the Kume River and the polluted water of the Tsuge and Yatani rivers, tributaries of the Hattori River. When we examined whether THMFP and MFP depended on the concentrations of organic substances in water, both potentials highly correlated with chemical oxygen demand (COD) in all water samples surveyed. The correlation coefficients between COD and THMFP and between COD and MFP were 0.957 (n ϭ 76, P Ͻ 0.01) and 0.804 (n ϭ 76, P Ͻ 0.01), respectively.