Clinical isolates of Proteus mirabilis causing catheter encrustation and blockage are susceptible to the biocide triclosan (MICs of 0.2 mg/liter). Studies with laboratory models of the bladder have demonstrated that the inflation of catheter retention balloons with triclosan solutions rather than water results in the diffusion of triclosan from the balloons into the surrounding urine and the inhibition of catheter encrustation by P. mirabilis. The aim of this study was to test whether the exposure of P. mirabilis to triclosan under laboratory conditions resulted in the selection of strains with reduced susceptibilities to this biocide. Exposure to triclosan in agar was shown to select mutants with MICs elevated from 0.2 mg/liter up to 80 mg/liter. In a selection of 14 of these strains, the decreased susceptibility was found to be stable and not associated with increased resistance to antibiotics. Experiments with the laboratory models demonstrated that inflation of the catheter balloons with triclosan (10 mg/ml) prevented encrustation and blockage by the parent strain P. mirabilis B2 (MIC, 0.2 mg/liter) and the mutant strain M48 (MIC, 2.0 mg/liter) but had no effect on crystalline biofilm formation by strain M55 (MIC, 40 mg/liter). These results suggest that, in any clinical trial or subsequent clinical use of the strategy, it will be important to monitor the urinary flora of the catheterized patients for P. mirabilis strains with reduced susceptibility to triclosan. The emergence of these strains could undermine the ability of the triclosan strategy to control catheter encrustation.