Amitriptyline was evaluated as a prophylactic antimigraine agent in 110 patients with severe migraine. This agent improved the migraine more than 50 percent in 72 percent of patients and more than 80 percent in 57 percent of patients. Most of the 31 patients with less than 50 percent improvement had virtually no response. Depression, measured with the Zung Self-Rating Depression Scale, was absent in 40 patients, borderline in 53, and moderate to severe in 17. Overall, depression ratings improved minimally with therapy. There was a weak relationship between improvement in depression and improvement in migraine. Subgroups with a stronger correlation of these could not be found. This work suggests that amitriptyline is effective in migraine prophylaxis and that it has a primary effect on migraine that is relatively independent of its antidepressant action.