Genetic contamination of mouse strains is an important concern for mouse breeding colonies in general, and a comprehensive discussion is beyond the scope of this manual. However, because germ-free mouse colonies are small and housing space is highly constrained, breeding germ-free mice presents some unique challenges that are worth discussion. Genetic contamination can be of roughly two types: genetic drift and inadvertent crossbreeding. Genetic drift occurs when mouse lines are propagated for many generations.1-3 In large breeding colonies, it can be monitored and managed. In germ-free colonies, however, because of the limited number of breeding pairs available and the limited resources of most small operations, it is largely ignored. It likely does occur and should be a consideration in choosing control strains for experimentation, but it is not further considered here. Further information is available in the literature2,3 and online (https://jaxservices.jax.org/genome/index.html, https:// jaxmice.jax.org/genetichealth/GQCprogram.html).