Diagnosis of sylvatic plague in a captive black-footed ferret (Mustela nigripes) was based on gross and microscopic lesions, fluorescent antibody tests, culture of Yersinia pestis, and immunohistochemistry. Gross lesions consisted of acute hemorrhage and necrosis associated with cervical and mesenteric lymph nodes, subcutaneous hemorrhages, and pulmonary edema. Acute edema, hemorrhage, and necrosis with numerous bacteria in blood vessels and sinusoids characterized microscopic lesions. Occurrence of fatal plague in a black-footed ferret potentially has significant implications for recovery of this endangered species due to the widespread distribution of plague in prairie dog colonies throughout historic black-footed ferret range.