The detection of external and internal parasites in laboratory mice is a particularly problematic aspect of animal health evaluation. Because these organisms must be detected by direct examination of the feces or hair coat, low-level infestation or sporadic shedding can make them difficult to detect, thereby undermining confidence that negative reports are truly negative. Prophylactic treatment of suspect colonies with anthelminthics and/or insecticides may therefore be indicated under some circumstances. However, when considering the use of prophylactic treatments, the potential for toxicity is an important factor, especially in genetically modified strains of mice. To evaluate the potential toxicity of prophylactic anti- parasitic treatments on strains of mice that are commonly used as experimental models and in genetic engineering in our facility, we surveyed a number of strains and ages of mice for toxic reactions during treatment regimens that combine anthelminthic and anti-acaricidal agents. Three experimental protocols (ivermectin, piperazine, and dichlorvos in combination; ivermectin alone; and fenbendazole/permethrin or fenbendazole/dichlorvos) were evaluated. Our data suggest a potential for toxicity associated with these treatments and indicate to us that prophylactic treatment regimens should be initiated with caution.