Clomipramine, metoprolol, or placebo was administered to 36 migraine patients in a double-blind crossover study. The patients were randomly assigned to one of the following five treatment groups: group 1 (clomipramine followed by placebo), group 2 (placebo followed by clomipramine), group 3 (metoprolol followed by placebo), group 4 (placebo followed by metoprolol), and group 5 (clomipramine followed by metoprolol). Dosage form was the same in all groups. The study de sign consisted of a 6-week baseline period, administration of first drug for 4 weeks, a 4-week washout period, administration of second drug for 4 weeks, and a 6-week followup period. Headache variables such as attack frequency as well as headache intensity and duration were recorded daily in diaries. The data were evaluated by time series analysis (ARIMA). Only metoprolol significantly reduced attack frequency and headache duration. Adverse reactions to clomipramine were severe. Our results showed metoprolol to be an effective antimigraine drug.