Canine monocytic ehrlichiosis (CME) is a potentially fatal tick-borne disease caused by the rickettsia Ehrlichia canis (16). The etiologic agent was first recognized in Algeria in 1935 (8). Since then, it has been reported worldwide, causing extensive morbidity and mortality among domestic dogs and other canids (11, 28, 51). The principal vector of CME is Rhipicephalus sanguineus (11). Recently, it has been shown experimentally that Dermacentor variabilis is also capable of transmitting E. canis (24). The pathogenesis of CME consists of an incubation period of 8 to 20 days, followed sequentially by acute, subclinical, and in some cases chronic phases. The disease may be manifested by a wide variety of clinical signs of which depression, lethargy, weight loss, anorexia, pyrexia, lymphadenomegaly, splenomegaly, and bleeding tendencies are the most common. Principal hematologic abnormalities include thrombocytopenia, mild anemia and mild leukopenia during the acute stage, mild thrombocytopenia in the subclinical stage, and pancytopenia in the severe chronic stage. The main biochemical abnormalities include hypoalbuminemia, hyperglobulinemia, and hypergammaglobulinemia (16). CME has been researched extensively in the last decade, and special efforts have been made to elucidate the pathogenesis of the disease. Better understanding of major mechanisms involved in the pathogenesis of the disease may assist clinicians in understanding the disease process and providing appropriate treatment, affording a better prognosis to their patients. In the light of the recent emergence of similar ehrlichial pathogens that infect human patients, the understanding of pathogenic processes in CME may contribute to the understanding of human monocytic ehrlichiosis and human granulocytic ehrlichiosis. This article reviews recent investigations in the pathogenesis of CME with special reference to platelet disorders and serum protein alterations, the principal hematological and biochemical abnormalities in CME, respectively. Host immune response in both acute and persistent E. canis infection is discussed and is proposed to be involved in the pathogenesis of disease manifestations.