Valproic acid and its enteric-coated derivative, divalproex sodium, have been used extensively in a wide variety of seizure disorders. Recent preliminary research demonstrates the effectiveness of valproate in the treatment of manic-depressive illness, including acute mania, prevention of bipolar episodes, and schizoaffective disorder. In uncontrolled and controlled studies, treatment-resistant patients with these disorders have responded well to valproate. Preliminary results of an ongoing community-based open trial of valproate treatment of those affective illnesses reveal that valproate is frequently effective and has a favorable side effect profile. Overall, approximately two out of three patients with refractory bipolar disorder respond to acute therapy with valproate. Response in schizoaffective patients has been moderate, and valproate seems to be less effective in the treatment of depression. Experience suggests the importance of monitoring plasma drug levels to maximize efficacy and minimize potential toxicity.