We studied the effect of parenteral pulse cyclophosphamide therapy in nine patients with active systemic lupus erythematosus and severe central nervous system involvement. Seven patients had focal neurological deficits and/or seizures associated with abnormalities on cerebrospinal fluid analysis and/or magnetic resonance imaging. Two patients had organic brain syndrome with psychosis and normal cerebrospinal fluid and/or magnetic resonance imaging analysis. Six patients were unresponsive to treatment with high dose corticosteroid. Cyclophosphamide, 0.75-1.0 g/m2 body surface area, was administered intravenously every month for at least 2 months. Eight patients had a complete recovery or recovered with minor residuals. Cyclophosphamide was well tolerated with few side effects. We conclude that parenteral pulse cyclophosphamide is an effective adjunctive therapy for the management of patients with active systemic lupus erythematosus and central nervous system symptoms.