At this time, hemorrhagic fever with renal syndrome remains one of the most common infectious diseases in the Russian Federation. An active natural focus of HFRS is the Voronezh region, where the natural reservoir of hantaviruses and the source of infection for people are wild rodents — bank vole, field mouse, and gray vole. The highest incidence rates of HFRS in the Voronezh region were recorded in 2019, significantly exceeding the rates of other years. The article presents data on the features of the epidemiology of HFRS and analyzes in detail the characteristic clinical manifestations of the disease. Important epidemiological aspects of hantavirus infection in the Voronezh region are the summer-autumn seasonality, the predominance in the structure of sick young men of working age living within the city. The pronounced summer-autumn seasonality of HFRS is due to contacts of patients with natural objects in both foci of infection. The clinical picture revealed a cyclical course of the disease, prolonged febrile-intoxication syndrome, enlarged liver and spleen, hemorrhagic syndrome, signs of renal pathology, thrombocytopenia. At the initial stage of the disease, typical manifestations of infection — symptoms of kidney damage, hemorrhagic manifestations, ophthalmological complaints, dry mouth and thirst — are rare or not clearly expressed. The studied features of the epidemiological aspects and clinical manifestations of HFRS in the Voronezh region are of great practical importance for differential diagnosis and early diagnosis at the prehospital stage for the purpose of timely hospitalization of the patient.