Six cases of apparent and four cases of histopathologically confirmed vasculitis of the central nervous system (CNS), including one case of histopathologically documented vasculitis with encephalitis associated with coccidioidal meningitis (CM), are presented. Vasculitic complications included changes in mental status as well as stroke-like findings of aphasia, hemianopsia, and hemiparesis. Seven patients died. Vasculitic complications were unanticipated and often abrupt in onset, and delayed therapeutic intervention was characteristic. The diagnosis of vasculitis/encephalitis due to Coccidioides immitis infection must be based on clinical judgment, since serum antibody titers, cerebrospinal fluid findings, and initial radiological studies are not always helpful. Institution of both intravenous and intracisternal administration of amphotericin B and possibly concomitant intravenous administration of dexamethasone may be warranted in situations in which the association of C. immitis with CNS vasculitis or encephalitis appears likely before serologic or cultural confirmation of C. immitis infection involving the CNS is available.