A 6-year-old, female, spayed Scottish Terrier weighing 13 kg was referred to the Colorado State University Animal Cancer Center (CSU-ACC) for radiation therapy (RT) for refractory multicentric lymphoma. The University of Wisconsin (UW)-Madison protocol (cyclophosphamide, a doxorubicin, b vincristine, c asparaginase, d and prednisone e ) 1 was initiated 1 year before presentation at CSU-ACC. A complete remission was achieved after the 1st dose of chemotherapy and continued for the next 11 months. When relapse was detected, a modified UW-Madison protocol substituting actinomycin D f for doxorubicin was initiated. The dog received 1 cycle of this modified protocol before the disease progressed. Asparaginase was administered 1 week before presentation at CSU-ACC. Additional rescue chemotherapy protocols were considered, but the owners opted for RT referral in an attempt to reduce tumor burden.The most predominant features on general physical examination were generalized lymphadenopathy, hepatomegaly, and splenomegaly. The dog was otherwise clinically normal without signs of gastrointestinal upset or lethargy. The dog was not receiving other medications. A CBC revealed mild thrombocytopenia (115,000/ uL; reference range, 200,000-500,000/uL). A serum biochemistry profile obtained 1 week before presentation at CSU-ACC had high alkaline phosphatase (2,000 U/L; reference range, 23-212 U/L) and high alanine transferase (517 U/L; reference range, 10-100 U/L) activities. All other values were within reference range. Hepatomegaly and splenomegaly were evident on left lateral thoracic and abdominal radiographs obtained for RT planning.The plan was to administer two 3-Gray fractions to the entire body on consecutive days. Whole body radiation was planned instead of the more common half-body RT protocol because of the concern that if only half the body was irradiated, the dog's disease would remain in the half of the body that was not irradiated. To help spare as much bone marrow as possible, the dorsal aspect of the cranium, the vertebrae, tail, and the distal radii, ulnae, and tibiae were not included in the radiation field. Acute tumor lysis syndrome (ATLS) after half-body radiation therapy in dogs with lymphoma has been documented. 2,3 In addition, this dog had several risk factors known to promote ATLS development, such as a large tumor burden and abdominal disease. The owners were counseled on the high risk of this dog developing ATLS because of the treatment modality employed as well as known risk factors this dog possessed. The owners opted to continue with the treatment plan. The dog received one 3-Gray fraction of 6-mV photons from a linear accelerator. g Four hours after treatment, emesis and diarrhea developed. The dog was febrile (104.7uF; reference range, 99.0-102.5), tachycardic (140 beats per minute), and tachypneic (70 breaths per minute). Mucous membranes were pale pink and tacky with capillary refill time less than 2 seconds. Femoral pulses were weak. Results of a serum biochemistry profile during this time...