Meningitis and encephalitis are inflammatory syndromes of the meninges and brain parenchyma, respectively, and may be identified either by finding definitive evidence of inflammation on tissue pathology or by cerebrocpinal fluid (CSF) analysis showing pleocytosis or intrathecal antibody synthesis. Clinicians evaluating undifferentiated meningitis or encephalitis should simultaneously consider autoimmune, infectious, and neoplastic causes, using patient risk factors, clinical syndrome, and diagnostic results including CSF and MRI findings to narrow the differential diagnosis. If an autoimmune cause is favored, an important early diagnostic question is whether a specific neural autoantibody is likely to be identified.