An open trial of long-term prophylactic therapy with Verapamil (240 mg/day) was completed in 44 patients with different types of chronic headache including: classic migraine (N = 15), common migraine (N = 11 ), cluster headache (N = 14), and muscle contraction headache (N = 4). Results were compared with similar trials utilizing Nifedipine and Nimodipine. Cerebral blood flow was measured before and after treatment. All three drugs block Ca 2+ entry into vascular smooth muscle and were effective in prophylactic treatment of migraine and cluster headaches but not in muscle contraction headaches. Treatment with Verapamil for 2-3 weeks abolished or attenuated migraine prodromes, decreased headache frequency in cluster and classic migraine, but were less effective in common migraine. Cerebrovascular resistance was significantly reduced by Verapamil, confirming its vasodilator effects. Side effects were less common with Verapamil than with Nifedipine and included postural hypotension, constipation and skin rash. Decreased efficacy after long-term treatment with Verapamil responded to dose increases. Experience in this laboratory with Nimodipine, Verapamil and Nifedipine indicates that all are effective in prophylactic treatment of vascular headache in that order of preference.