The aim of this double-blind crossover study was to compare the prophylactic effect of acetylsalicylic acid (ASA) with that of propranolol (PRP) in the treatment of migraine. Plasma concentrations of the two drugs were measured in order to investigate a possible relationship to the clinical effect. Compared to the pretreatment period, PRP and ASA reduced migraine index, frequency, duration, severity of attacks and headache days. Due to the limited number of patients, our results should be cautiously interpreted, however relevant the clinical improvement seemed. Improvement of migraine index was not related to different plasma levels of the two drugs.