The unique experience of plague control in its natural foci was accumulated in the Soviet Union in the 1930s-1970s. At that period the main measure taken for conditioning these foci was the extermination of rodents, the main carriers of plague, and their fleas as vectors with the aim of breaking, as it was then believed, the continuous process of the transmission of Yersinia pestis among rodents. These measures, carried out in many natural foci for several decades, did not bring desired results; in none of these areas natural foci of plague could not be liquidated, completely or in part. The experience of the anthropogenic transformation of the landscapes of the natural foci of plague revealed that the best antiplague effect was obtained after vast territories were completely plowed up and used afterwards annually for monoculture. The accumulated experience of the prophylaxis of plague is indicative of the possibility of economic activity in the presence of active natural foci of plague on condition that epidemiological surveillance is carried out on the necessary scope.