Due to its multiple physiologic effects, including interference with vasoconstriction, protection against brain hypoxia, antihistaminic activity and serotonin antagonism, Flunarizine, a calcium channel blocker, is being considered as an agent for the prophylactic treatment of migraine. Twenty patients with classical or common migraine were treated for 2-6 months with a single nighttime dose of 10 mg of Flunarizine after a 1-3 month placebo stabilization period in a single blind crossover study. Seventeen patients experienced a statistically significant reduction in headache incidence and/or severity (average reduction 53.3%). No clinically significant changes in laboratory analysis, ECG, or physical examination occurred during the treatment period. Side effects included weight gain, dry mouth, fatigue, sleepiness, muscle aches, and paresthesias, and prompted discontinuation of Flunarizine in three patients. We conclude that Flunarizine may be an effective agent in migraine prophylaxis in certain patients. Its low incidence of generally mild side effects may make it preferable to many of the agents currently in use.