An ultrasonographic reproductive health examination of a 26-yr-old female African elephant (Loxodonta africana) revealed bilateral ureteral wall thickening and dilatation. On ultrasonographic examination, the bladder and both ureters were normal near the trigone; however, the cranial-most aspect of each ureter was dilated and thickened for a length of 30–50 cm. The same month, elevated blood creatinine (3.0 mg/dl), and urine protein-creatinine ratio (4.0) were observed. Chronic renal failure was diagnosed based on these abnormalities, and the persistent ureteral dilatation was seen on subsequent ultrasound examinations. Complete blood cell counts, serum chemistries, and urinalyses remained relatively unchanged until 24 mo after diagnosis, at which time azotemia, hypophosphatemia, and hypercalcemia (including elevated ionized calcium) developed. Hydronephrosis of both kidneys and prominent sacculation of the left ureter were noted on ultrasonographic examination. Lethargy, ventral edema, and oral mucosal ulceration acutely developed 30 mo after diagnosis. Although blood urea nitrogen remained elevated, creatinine, total calcium, and ionized calcium returned to within reference ranges at that time. Due to rapid clinical decline and grave prognosis, humane euthanasia was elected. Bilateral ureteral dilatation, dysplasia of the right kidney, and chronic nephritis of the left kidney were identified postmortem.