Sixteen healthy cats were fed a 6-wk-old laboratory mouse that had died of experimentally induced Yersinia pestis infection (strain NM77-538), to simulate oral exposure to plague. The cats were closely monitored after ingestion. Physical exams were performed and vital signs were recorded daily. Plague antibody titers and cultures of blood, throat, and oral cavity were performed daily. Complete blood counts and biochemistry panels were performed every 3 d. Complete necropsies were performed on any cats that died. Cats exhibited one of three responses following ingestion of one plague-infected mouse; they either died (6/16 or 38%), developed transient illness and recovered (7/16 or 44%) or showed no signs of illness (3/16 or 19%). A continual fever greater > 40 degrees C was associated with a poor prognosis. The highest antibody titers developed in the group that shed the plague bacillus over an extended period of time. Blood, throat, and oral cavity cultures were positive in 100% of the fatal cases. Throat cultures were positive in 75% of the exposed cats. In contrast to other carnivores, cats infected with Y. pestis exhibit bubo formation and pneumonic lesions similar to those seen in people with plague. Because of the potential transmission of Y. pestis from cats to people, development of a plague vaccine for cats may be warranted.