Cytauxzoonosis, caused by Cytauxzoon felis, is a regionally common, often fatal tick-borne disease primarily affecting the domestic cat. Retrospective analysis of case records from January 1995 to June 2005 identified 148 domestic cats diagnosed with cytauxzoonosis, having suitable archived lung sections. Lung sections were examined and graded on relevant parameters, the chief purpose of which was to characterize the pulmonary lesion of fatal feline cytauxzoonosis. Parameters were scored 0 to 3 for no lesion, mild, moderate, and severe, respectively. Evaluated parameters included the presence of interstitial pneumonia, increases in number of alveolar macrophages, degree of intra-alveolar hemorrhage, neutrophils infiltrating peribronchial and septal interstitium, and degree of vascular occlusion. Overall, interstitial pneumonia was moderate (1.72 +/- 0.65); alveolar macrophage numbers were mild (1.20 +/- 0.60); and intra-alveolar hemorrhage was mild (0.78 +/- 0.75). Neutrophil infiltrates were moderate (1.89 +/- 0.76), and vascular occlusion was moderate to severe (2.26 +/- 0.61). Pulmonary edema was common; its scoring was incorporated into the assessment for interstitial pneumonia. Interestingly, a thrombus was detected in the lung of 1 cat. The current understanding of the pathogenesis of cytauxzoonosis focuses on vascular occlusion by macrophages distended by megaschizont parasite stages within liver, spleen, and lung. These findings corroborate the current understanding yet shed light on the possibility that macrophage activation and inflammatory mediators lead to an interstitial pneumonic process characterized by neutrophilic infiltrates and pulmonary edema. These characterized lesions are likely correlative with the respiratory distress seen in affected cats.