Most rheumatologic and vasculitic syndromes can affect the central nervous system (CNS). In the vast majority of cases, however, the systemic disease is present at the time of first CNS manifestations. Certain of these diseases, including SLE, PSS, Behçet syndrome, cryoglobulinemia and lymphomatoid granulomatoses can present with CNS findings in the absence of any peripheral evidence of the underlying process. The CNS presentations of these and the other rheumatologic and vasculitic syndromes which may affect the CNS are discussed. Isolated CNS vasculitis may be due to granulomatous angiitis of the nervous system (GANS) or delayed contralateral hemiplegia following HZO. These are distinct clinical entities which can be differentiated by clinical and angiographic findings. The former is often severe and diffuse in nature, whereas the latter is usually milder and more focal. There are few if any peripheral findings in either syndrome. The cause of GANS is unknown, but the hemiplegia following HZO is clearly due to a virus-induced vasculitis spread from the overlying Gasserian nucleus; the history of preceding herpes zoster ophthalmicus strongly suggests the diagnosis. The collected evidence suggests that an aggressive evaluation, including meningeal biopsy, and early therapy with steroids (and perhaps cytotoxic agents) can alter the prognosis in GANS. It is not clear that hemiplegia following HZO requires treatment. GANS and HZO-associated CNS damage should be considered in the differential diagnosis of isolated CNS dysfunction in the absence of history, signs, or laboratory abnormalities suggestive of systemic disease.