A 3-year-old female intact Miniature Australian Shepherd presented with convulsive status epilepticus after milbemycinoxime administration in the recommended dosage. In addition to continuous intravenous antiepileptic therapy the dog had to be ventilated for 36 hours due to aspiration pneumonia. After extubation control of intermittent tonic-clonic seizures required a constant-rate-infusion of propofol for another 96 hours, before it could be discontinued on day 5. The patient had fully recovered by day 10. The dog was known to be homozygous for the MDR1-gene mutation. So far milbemycinoxime was regarded a save drug in MDR1-deficient dogs. However, the present case suggests using the lowest possible dosage in MDR1-deficient dogs and pet owners should be advised of potential complications.