Chlorination/dechlorination is the most commonly applied form of disinfection for municipal wastewaters; however, important drawbacks to chlorine-based disinfection processes have been identified. The most common alternatives to chlorination/dechlorination are ozonation and UV irradiation.The City of Indianapolis is considering a switch from their existing chlorination/dechlorination operations to ozonation, UV irradiation, or a combination of these processes at their Belmont and Southport Wastewater Treatment Facilities. To examine the feasibility of these disinfection process alternatives, bench-scale experiments were conducted with effluent samples from each facility. The results of these experiments demonstrated that effluents from these facilities have high ozone demand, which promotes efficient transfer of ozone, but diminishes its disinfection efficacy. On the other hand, UV 254 irradiation yielded consistent compliance with effluent discharge permit limitations at UV 254 doses of 15-20 mJ/cm 2 , depending on pre-ozonation dose. No evidence of synergism between O 3 and UV 254 radiation was found in the measured inactivation responses of E. coli among the effluent samples from Belmont and Southport. The antimicrobial effects of these two disinfectants appeared to be additive for the range of disinfectant exposure conditions used in these experiments.The nature of the data sets collected in these studies is such that variability in several fundamental properties of the effluent samples could be defined. These data sets form the foundation of a new design protocol for UV systems, which is based on a stochastic approach, and that incorporates modern tools for prediction and measurement of UV process performance.This new design protocol has the potential to yield UV system designs that are not only reliable, but that also lead to process efficiency and reduced operating costs, relative to designs based on conventional protocols.