A free-ranging adult female great horned owl (Bubo virginianus) was presented to the Wildlife Medical Clinic at the University of Illinois after being observed with anorexia and decreased activity. A severe leukocytosis (212 400 cells/µl), primarily comprised of mature heterophils, was found at presentation. Results of various diagnostic tests including radiographs, Chlamydophila serologic testing, measurement of Aspergillus antibody and antigen titers, plasma protein electrophoresis, fecal culture and acid-fast staining, coelioscopy, endoscopy, tracheoscopy, exploratory coelomotomy, nuclear scintigraphy, tissue cultures, bone marrow biopsy, and histopathology revealed no underlying cause for the persistent leukocytosis. No response to treatment with antibiotics or aungal agents was observed, although a transient, significant decrease in the leukocyte count (6200 cells/µl) was observed after treatment with fenbendazole. A presumptive diagnosis of chronic myelogenous leukemia was made based on 3 factors: disease duration of greater than 3 months, a lack of ideiable foci of inflammation, and a lack of response to conventional therapy. The diagnosis was confirmed based on postmortem examination and testing 177 days after initial presentation.