A systematic trial of Cocaine hydrochloride as an abortive therapeutic agent in cluster headache is presented. Headache induction was performed with sublingual Nitroglycerin (1.0 mg) and cocaine was employed for abortive purposes. Subjects were then instructed in a mode of self-application of cocaine solution to their Sphenopalatine Foramen regions for abortion. Most patients can learn to abort most of their cluster headaches by application of cocaine solution to their Sphenopalatine Foramen region in from 15 seconds to three minutes. The risk of addiction is slight when employing 5 to 10% solution for the period of time that the typical cluster persists (4–12 weeks), and the benefits are great in cessation of the agonizing pain that accompanies this headache. Cocaine may be a valuable adjunctive abortive therapeutic measure in cluster headache when combined with a patient educational program. The rapidity of its effectiveness in some circumstances might suggest that the origin of much of the pain of cluster headache may be found in the Pterygomaxillary Fossa region.