The potential therapeutic effect of sodium valproate (VPA) on the prophylaxis of migraine was assessed in 62 consecutive patients with severe migraine with and without aura subjected to an open label trial. Patients were given 400 mg VPA daily, divided in two oral doses, during 3 months and then asked to withdraw the drug for 3 months. The therapeutic response was measured with a scale of 15 items that assess the frequency and severity of migraine attacks, and the possible toxic side-effects were monitored by determinations of blood cells, liver enzymes, serum ammonia levels, and plasma VPA levels. Results indicate that 69.8% of patients obtained substantial benefit from this drug and that this beneficial effect lasted for at least 3 months after drug withdrawal in 67.6% of cases. No significant correlation was found between VPA levels and the therapeutic response as measured by the Migraine Assessment Scale. No serious side-effects were observed during the trial. Low-dose VPA is a safe alternative in the prophylaxis of severe migraine.