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Cryptosporidium oocysts are highly resistant to conventional chlorine-based disinfectants. An innovative method using ultraviolet irradiation was tested at full-scale (400 gpm) for its ability to inactivate Cryptosporidium oocysts. In vitro surrogates (excystation, DAPI/PI and the SYTO dyes) indicated at least 2-log inactivation based on the limitations of those assays. Animal infectivity studies using the neonatal mouse model showed a >4-log inactivation of Cryptosporidium in three separate trials. The technology appears to be a novel way to treat drinking water and provide an additional significant barrier in protecting public health.