Materials on the situation in quarantine natural focal infections (anthrax, plague, tularemia, brucellosis, leptospirosis, etc.) in the Southern Federal District are presented. Experience in the provision of the epidemic safety in the above-mentioned diseases, based on the systematic surveillance on the activity of epizootological factors on the territory of the natural foci of infections, are described. The causes of the possible aggravation of the epidemiological situation in a number of nosological forms in connection with changes in natural and socio-economic factors are given. The results of the realization of regional programs, making it possible to improve the system interaction between the administrative territories, services and departments aimed at ensuring the epidemiological safety of the region, are shown.