ABSTRACT- 22 patients with severe migraine resistent to previous prophylactic treatments participated in a prospective open trial of valproate in migraine prophylaxis; 17 had common and 5 classic migraine. The attack frequency was from 4 to 16(30)/month (1 patient suffered from attacks every day). The dose of valproate was 600 mg twice a day from start of treatment, successively adjusted to a serum level about 700 μmol/1. Follow-up was from 3 to 12 months; 11 patients were free from migraine attacks, 6 had a significant reduction of the frequency; in one patient there was no effect; 4 dropped out because of lack of cooperation; 3 who had been free from migraine for 3 months, participated in a withdrawal experiment during which they all experienced relapse. After reinstitution of valproate the attacks disappeared again. How valproate acts in migraine prophylaxis is not known, but this prospective open trial demonstrates that valproate has an appreciable prophylactic effect in patients suffering from severe migraine, and calls for controlled clinical trials.