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An 8-year-old female Labrador dog was anesthetized for contrast-enhanced computed tomography. The dog was sedated with dexmedetomidine and butorphanol and anesthetized with propofol and isoflurane. Upon IV injection of iohexol 350 mg/mL (72 mL), tachycardia, hypotension, and lower airway obstruction developed. Severe hypersensitivity to the contrast agent was suspected. Bronchospasm was treated successfully with epinephrine. Phenylephrine was used for pressure support. While rare, severe hypersensitivity to iodinated contrast agents can occur without evidence of prior exposure.