Intoxication with anhydrous ammonia (AA) is a common occupation-related health problem affecting farmers and fertilizer applicators, however, very few descriptions of animal exposure to this toxicant exist. Thieves entered a feedlot and damaged a liquid AA storage tank, resulting in the accidental leakage of gas from a valve. Overnight, 12 cattle were found dead, with a total mortality of 64 cattle out of 260 on the premises dying or euthanized in < 1 week. Signs of affected cattle included blindness, drooling, inappetence, respiratory distress, recumbency, and death. Two cattle were submitted live for diagnostic evaluation 3 days after initial exposure. Gross lesions included corneal ulcers, fibrinonecrotizing rhinitis, hemorrhages within the nasal sinuses, and anterioventral bronchopneumonia. Microscopic lesions consisted predominantly of degeneration and necrosis of superficial epithelium lining nasal passages, trachea, and pulmonary airways. This case illustrates the acute AA effects on cattle, which is likely to be an increasingly encountered problem because of on-farm storage of AA and its access by illicit drug manufacturers.