The prophylactic effect of a 5-HT uptake inhibitor, femoxetine, was compared with that of propranolol in a double-blind crossover study of 6-months duration. 29 patients commenced the experiment. 3 subjects withdrew because of side effects and 2 because the program was inconvenient for them. In the 24 patients who continued the study to the end, the periods of propranolol (administered 160 mg daily) and of femoxetine (given 400 mg daily) differed significantly from each other with respect to the attack frequency and headache index. A significant reduction in the use of medication relieving attacks was observed during the propranolol treatment as compared with the pre-treatment period. The study showed that partial depletion of thrombocyte 5-HT uptake inhibitor did not lead to a marked improvement in headache, contrary to what might be expected on the grounds of the 5-HT hypothesis of migraine.