Plague is widespread among rodents and their fleas in the western United States, but most human cases occur in several definable, ecologically unique, and geographically limited high risk areas in the Southwest and Pacific Coast states. Control strategies to prevent human cases in high risk areas must vary from one epizootic focus to another, depending on such basic ecological factors as rodent/flea species involved; their distribution, abundance, seasonality, and relationship with the plague organism; climatic factors that affect transmission; the lifestyles of human residents; and others. This paper briefly summarizes preliminary results of a long-term program to define human risk and develop effective surveillance and control measures against plague in a north-central New Mexico plague focus.