An epidemic of hemorrhagic fever with renal syndrome (HFRS) occurred in Yugoslavia May–November 1986; all Republics and Provinces were involved. Serum samples were received from 260 of 276 persons with symptoms clinically compatible with a diagnosis of HFRS. Presumptive infection with a hantavirus was determined serologically for 161 of these. Many patients with serious clinical pictures, including severe renal insufficiency and shock, were hospitalized; 11 died. Indirect fluorescent antibody tests with antigens of 4 hantaviruses (Hantaan, Fojnica, Puumala, and the Vranica strain of Puumala virus) showed that > 1 serotype was circulating during this epidemic. Hantavirus antigens were detected in the lungs of 86 of 302 (28.5%) wild-caught small mammals.