Interferon-beta (INF-beta) is effective and used in reducing exacerbation frequency and disease progression in multiple sclerosis. In certain circumstances, INF-beta can lead to rare side effects. We report the case of a 34-year-old female patient satisfying the McDonald criteria of multiple sclerosis without showing typical pathologic changes in cerebrospinal fluid (CSF). After introduction of INF-beta treatment, she quickly developed further progression of her disseminated neurological symptoms and finally an ischemic cerebral infarction. Evaluation of the patient included arterial angiography, magnetic resonance and positron emission tomography, histopathological assessment as well as a broad spectrum of serum and CSF analysis. All diagnostic evaluations and the clinical course revealed evidences for a primary angiitis of the CNS. We discuss the possible worsening due to inappropriate INF-beta treatment in cerebral angiitis promoting severe cerebrovascular insufficiency. The authors suggest that all diagnostic multiple sclerosis criteria including typical CSF findings should be ascertained before INF-beta treatment is initiated.