Surveillance of the natural foci of Especially Dangerous Infections (EDI) is necessary due to their etiological, epidemiological, and clinical diversity, their global spread and overall negative impact on public health. Some EDI pathogens with natural foci are also potential agents for biological weapons. Study of the EDI characteristics is important for development of an effective epidemiological protection system. Francisella tularensis is one of the most virulent human microorganisms and a critical Category A biological agent. In Ukraine, tularemia natural foci are registered in 23 of the 25 regions. We conducted integrated ecological-epidemiological and microbiological research on the EDI natural foci for the past 20 years.