The objective of this experiment was to test the potential of a combined water wash and cetylpyridinium chloride (CPC) treatment as a hide intervention applied to cattle in the holding pens of a processing plant immediately before stunning. Over 2 processing days, 149 control and 139 treated cattle were tested. Control cattle were processed in the normal manner. The treatment group was prewashed with water the day before harvest. Immediately before stunning, these cattle were sprayed twice with 1% CPC, rst for 3 min, then for 1 min. Hides and preevisceration carcasses were sampled to determine aerobic plate counts, Enterobacteriaceae counts (EBC), and Escherichia coli O157 prevalence. The treatment reduced the prevalence of E. coli O157 on hides from 56% to 34% and the prevalence on preevisceration carcasses from 23% to 3%. The treatment decreased aerobic plate counts from 4.9 log CFU/100 cm 2 to 3.4 log CFU/100 cm 2 and EBC from 3.1 log CFU/100 cm 2 to 2.0 log CFU/100 cm 2 on preevisceration carcasses. The treatment of hides did not result in any detectable CPC contamination of the chilled carcasses. These data indicated that a 1% CPC treatment preceded by a water wash was capable of reducing hide prevalence of E. coli O157 from as high as 80% to less than 50%, resulting in preevisceration carcass prevalence of 5% or less. We conclude that water washing followed by an antimicrobial treatment, such as CPC, has great potential as an effective hide intervention step and should be further evaluated for implementation as a processing step after stunning and before hide removal.