Efficacy of drugs for the acute treatment of migraine in children has not so far been studied in well controlled trials. We conducted a study to evaluate the efficacy of acetaminophen and ibuprofen. Eighty-eight children, aged 4.0 to 15.8 years, with migraine participated in a double-blind crossover study. Three attacks per child were treated in random order with single oral doses of 15 mg/kg acetaminophen, 10 mg/kg ibuprofen, and placebo at home. The primary end point, reduction in severe or moderate headache (grade > or = 3 on a scale of 1 to 5) by at least two grades after 2 hours, was reached twice as often with acetaminophen and three times as often with ibuprofen as with placebo. Ibuprofen was twice as likely as acetaminophen to abort migraine within 2 hours. In the intent-to-treat analysis, children improved twice as often with ibuprofen and acetaminophen as with placebo. Both ibuprofen and acetaminophen are effective and economical treatments for severe or moderate migraine attacks in children. Ibuprofen gave the best relief.