We designed a 3-month open label trial of melatonin prophylaxis in children with primary headache. After a one month baseline period without receiving preventive drugs, all children received a 3-month course of melatonin, 3 mg, administered orally, at bedtime. A total of 22 children were enrolled (10 boys, mean age 12.2+/-2.6 years, age range 6-16 years), 13 had recurrent migraine without aura, 1 with aura and 8 had chronic tension-type headache. When the trial ended, 14 of the 21 subjects reported that the headache attacks had decreased by more than 50% in respect to baseline and 4 of them reported having no headache attacks. After receiving melatonin for one month one subject dropped out because of excessive daytime sleepiness. Our promising results warrant randomized placebo-controlled trials in children to assess the real effectiveness of melatonin in preventing primary headache.