Potomac horse fever, a disease characterized by fever, anorexia, leukopenia, and occasional diarrhea, is fatal in approximately 30 percent of affected animals. The seasonal occurrence of the disease (June to October) and evidence of antibodies to the rickettsia Ehrlichia sennetsu in the serum of convalescing horses suggested that a related rickettsia might be the causative agent. Such an agent was isolated in cultured blood monocytes from an experimentally infected pony. This intracytoplasmic organism was adapted to growth in primary cultures of canine blood monocytes. A healthy pony inoculated with these infected monocytes also developed the disease. The organism was reisolated from this animal which, at autopsy, had pathological manifestations typical of Potomac horse fever. Cross serologic reactions between the newly isolated agent and antisera to 15 rickettsiae revealed that it is related to certain members of the genus Ehrlichia, particularly to Ehrlichia sennetsu. Since the disease occurs in other parts of the United States as well as in the vicinity of the Potomac River, and since it has also been reported in Europe, the name equine monocytic ehrlichiosis is proposed as being more descriptive.