Call-Fleming syndrome is a reversible segmental vasoconstriction of cerebral arteries manifested by a "thunderclap" headache and focal neurologic symptoms. Although of unknown etiology, it has been reported in association with vasoactive sympathomimetic drugs. The authors report Call-Fleming syndrome in two patients with history of antidepressant use. Although the association is hypothetical, the authors suggest consideration of Call-Fleming syndrome in patients presenting with headache, focal deficits, and evidence of cerebral ischemia during antidepressant use.