Status epilepticus is commonly refractory to first-line therapy, and thus better treatments are needed. We have investigated an experimental model of drug-resistant self-sustaining status epilepticus (SSSE) induced by 2 hours of perforant path stimulation. Propofol in subanesthetic doses administered shortly after the end of stimulation and also after a further 3 hours of SSSE terminated the SSSE without recurrence. This finding calls for a trial of propofol in refractory status epilepticus and also raises the possibility of using it as first-line therapy.