Recognition of hepatozoonosis in four dogs that lived in Oklahoma their entire lifetimes documents expansion of the previously recognized endemic area of the disease. Salient clinical features are fever, marked neutrophilic leukocytosis, periosteal new bone proliferation, myalgia, weakness, muscle and generalized wasting, and lack of response to treatment. Transient, large-bowel diarrhea may be observed. Each of the four cases had signs compatible with chronic, persistent inflammatory disease that were poorly and ultimately nonresponsive to antimicrobial treatment. Diagnosis was confirmed in one case by recognition of Hepatozoon gamonts in peripheral blood leukocytes. Encysted forms of the organism were present in skeletal muscle and other tissues of each case.