In a double-blind study comparing crossover and parallel group designs, 55 patients with recurrent throbbing headache were given either belladonna-ergotamine-phenobarbital (BEP) or placebo for headache prophylaxis. Analysis of the crossover design showed BEP to be significantly more effective than placebo in reduction of headache severity and overall effectiveness. During BEP treatment, patients had less days during which medications for relief of headache symptoms were required. Although there were period effects favoring BEP, no significant differences between treatments were observed in the parallel design. The greater variability in the parallel portion of the study precluded demonstration of statistical significance with this number of patients. The crossover design indicates that BEP offers benefits in the prophylaxis of recurrent throbbing headache, without serious or frequent side effects.