We analyzed retrospectively the data for 300 patients with refractory headache who were treated with dihydroergotamine (DHE) at the Comprehensive Headache Center at Germantown Hospital. The patients had either chronic daily headache (with drug rebound -216, without rebound -42), short-duration headache (18), or cluster headache (24). Treatment consisted of withdrawal of overused medications (usually analgesics and ergots), repetitive IV administration of DHE, and use of metoclopramide and prophylactic medications, together with educational and psychological support. Overall, 91% (range, 86% to 100%) of the patients became headache-free, usually within 2 to 3 days. The average duration of hospitalization was 7.4 days. Side effects, reported in 157 (52%) of the patients, consisted primarily of nausea (32%), tightness and burning (8%), leg cramps (7%), vomiting (6%), and increased blood pressure (5%). The side effects generally resolved spontaneously or with adjustment of the DHE dose and/or adjunct medication, and necessitated withdrawal of therapy in only 2 patients (1 with drug-related claudication; 1 with somatic complaints of uncertain origin). We conclude that a regimen of repetitive intravenous DHE and metoclopramide can provide rapid relief of chronic intractable headache, and can ameliorate the effects of analgesic and ergot withdrawal in patients with chronic daily headache and rebound associated with overuse of these drugs.