The tribe Ehrlichieae consists of gram-negative minute cocci that are obligate intracellular parasites classified in the family Rickettsiaceae. Although ehrlichial organisms have been observed in leukocytes for many years, only a few species have been cultured in quantities sufficient for biochemical and molecular analyses. Recents studies on 16S-rRNA sequence analysis and energy metabolism showed that the genus Ehrlichia is closely related to the genus Rickettsia. There is, however, no antigenic cross-reactivity between these genera. Ehrlichial organisms cause a disease called "ehrlichiosis," a noncontagious infectious disease known to be transmitted by a tick in several cases and by a fluke in one case. Ehrlichia spp. infect dogs, ruminants, horses, and humans. Recently, two new ehrlichial diseases, Potomac horse fever and human ehrlichiosis, were discovered in the United States. The etiologic agent of Potomac horse fever, Ehrlichia risticii, is closely related to the known human pathogen Ehrlichia sennetsu. The etiologic agent of human ehrlichiosis is related to Ehrlichia canis, a canine pathogen. In contrast to the genus Rickettsia, members of the tribe Ehrlichieae reside primarily in the cytoplasmic vacuoles of monocytes or granulocytes and cause hematologic abnormalities, lymphadenopathy, and other pathologic changes in the host. However, the actual mechanisms whereby Ehrlichia spp. infect leukocytes, multiply in them, and produce various forms of systemic disease have not been defined. Depending on the ehrlichial species involved, serologic or direct microscopic observation of stained blood smears is currently used to diagnose ehrlichial disease.