Handling a rodent disease outbreak in a facility can be a challenge. After the University of Colorado Denver Office of Laboratory Animal Resources enhanced its sentinel monitoring program, > 90% of the animal colonies housed in a vivarium at the Anschutz Medical Campus (with an area of 50,000 net ft(2)), serving the labs of > 250 principal investigators, tested positive for multiple infective agents including mouse parvovirus, fur mites, pinworms and epizootic diarrhea of infant mice. The authors detail the process by which they planned and executed a shutdown and a decontamination of the facility, which involved the rederivation or cryopreservation of > 400 unique genetically modified mouse lines. The authors discuss the aspects of the project that were successful as well as those that could have been improved.