The feasibility of a “last moment” prevention of migraine with the selective dopamine receptor blocker domperidone (Motilium(r)) was evaluated in patients who experience typical, but minor prodromes several hours before the attack. Following a previous placebo-controlled trial, a dose-response study was done. In a randomized, double-blind cross-over setting, oral doses of 20 mg, 30 mg or 40 mg of domperidone were each given twice to 19 patients who were able to predict their attack several hours in advance. Taken at the very first appearance of the early warning symptoms, 20 mg, 30 mg and 40 mg prevented respectively 30%, 58% and 63% of the (imminent) attacks. Part of the attacks still occurring after domperidone, particularly after 20 mg, were reduced in severity. Irrespective of the dose given, the best response was observed when domperidone was taken 6 h, and even better, 12 h before the attack. Migraine-associated hypersensitivity of dopamine receptors might explain why dopamine blockade with domperidone is of benefit to the patient.