METHODS A 41-year-old man was admitted to the hospital because of a series of seizures. History revealed increasing weakness and generalized myalgia following a severe respiratory tract infection three months previously. The clinical examination was dominated by reduced alertness and cognitive impairment. METHODS Positive ANA titres pointed to an autoimmune disease; further laboratory tests revealed an antiphospholipid syndrome. The clinical diagnosis of systemic lupus erythematosus was supported by renal biopsy. Transcranial Doppler sono-graphy and magnetic resonance imaging with angiography revealed cerebral vasculitis with multiple intracerebral grey and white matter lesions. METHODS In addition to an immunosuppressive therapy with corticosteroids and intravenous pulses of high-dose cyclophosphamide, oral anticoagulation was given in order to prevent thromboembolic complications. Seizures were treated with valproate. A follow-up MRI revealed multiple glial cell reactions and reduced vasculitic changes. CONCLUSIONS Initial neuropsychiatric symptoms and seizures prompted the diagnosis of systemic lupus erythematosus with cerebral vasculitis in a 41-year-old patient. Approximately 20 % of all lupus patients initially present with neuropsychiatric disorders. Central nervous system involvement and renal complications determine the course and prognosis of the disease as well as therapeutic decisions. Particularly in young patients with neuropsychiatric symptoms systemic lupus erythematosus should be excluded routinely.