We undertook a prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of intramuscular parenteral chlorpromazine (CPZ) in the treatment of the acute migraine attack. Thirty-six patients who presented to the emergency department with migraine headache were given either CPZ (1 mg/kg) or a saline placebo and were observed for one hour. Of those receiving CPZ, nine of 19 (47.4%) had sufficient relief from their headache to carry on with their activities of daily living, compared with four of 17 (23.5%) of the control group. This difference was not statistically significant. However, the drug was more often effective than a placebo in giving some relief from the headache (P less than .005) and in relieving nausea significantly more often than placebo (P less than .001). The only significant side effects were drowsiness (P less than .01), and an asymptomatic drop in blood pressure (10 mm Hg systolic) (P less than .05). This controlled study demonstrates that CPZ is a safe medication that provides some relief from migraine headaches, but it is less efficacious than suggested in earlier reports.