Transnasal butorphanol (TNB) is a mixed agonist-antagonist opioid that has recently been released for the treatment of painful conditions. Patients with a history of migraine diagnosed in either of two emergency departments (EDs) with a moderate or severe migraine were eligible for this prospective study. Patients received 1 mg of TNB at time zero and again in 45 minutes if needed. Twenty-five patients were studied. Pain intensity was measured on a 10-cm visual analog scale. Mean pain intensity was significantly decreased at 15 minutes and declined from 7.9 +/- 1 cm initially to 2.5 +/- 3.3 cm at 90 minutes. Sixty percent of the patients required no further treatment. Thirty-six percent experienced side effects, with all but 1 being mild or moderate. Seventy-five percent rated the treatment as good, very good, or excellent, and 71% would prefer to receive TNB for future migraines over other treatment options. TNB offers rapid, effective pain relief to the majority of ED migraine patients.