Objectives: Since several anticonvulsants are therapeutic in mania and since acute mania requires rapid and intensive treatment, we hypothesized that intravenous high-dose phenytoin might be acutely antimanic. A new prodrug of phenytoin, fosphenytoin, which has few cardiac or local vein side effects, was used to test this hypothesis. Method: Seven patients with a DSM-IV manic episode and minimal prior drug treatment were given intravenous fosphenytoin and were assessed at baseline and after 15, 30, 45, and 60 minutes with the Young Mania Rating Scale, the Clinical Global Impressions scale, and the Mini-3Mental State Examination. Data were gathered in 2002. Results: No antimanic effects were observed. No subject had any clear improvement in manic symptoms on the YMRS at any timepoint assessed. Conclusion: Intravenous fosphenytoin at doses that are effective in status epilepticus appears to be ineffective in acute mania.