Chlorine dioxide was compared with chlorine for the disinfection of wastewater in laboratory experiments. Disinfection with chlorine dioxide was also demonstrated at a full-scale wastewater treatment plant. Criteria for comparison included coliform kill, inactivation of poliovirus and other indicators, and formation of halogenated organic by-products. In general, chlorine dioxide accomplished a given fractional kill of total coliforms with a smaller product (residual x time) than chlorine. The required mass doses of the disinfectants were approximately equal for treating conventional activated-sludge effluent. The required dose of chlorine was approximately 2 to 10 times greater than that of chlorine dioxide for treating filtered, nitrified effluent, depending on the coliform standard. Chlorine dioxide was found to be more effective for inactivating Polio-virus I and natural populations of coliphage in both non-nitrified and filtered, nitrified wastewater effluents. Chlorine dioxide treatment formed no measurable amounts of trihalomethane by-products, whereas chlorine treatment formed 0.5 to 5 micro Mol per liter of trihalomethanes, chiefly chloroform, in experiments using wastewater effluents. Based on a total coliform standard of 1000 per 100 ml disinfection with chlorine is estimated to cost 0.3 to 1.7 cents per cu m (1.1 to 6.4 cents per 1000 gallons), depending on plant size, compared with 1.5 to 3.5 cents per cu m (5.8 to 13.4 cents per 1000 gallons) for disinfection with chlorine dioxide (1979 price levels).