The hospital records of 78 patients who underwent surgical therapy for fungal infections of the central nervous system (CNS) between 1964 and 1984 are summarized. Nine different fungal types were identified, but Coccidioides immitis and Cryptococcus neoformans accounted for most (67.1%) of the infections. A variety of clinical syndromes were seen, including chronic basal meningitis (45 patients), intracranial mass lesions (12 patients), and communicating hydrocephalus (six patients). Thirteen patients had rhinocerebral forms of fungal infection, and two presented with spinal involvement. Delays in diagnosis were frequent and ranged from 2 months to 11 years. In 31 patients the CNS lesion was the first indication of a fungal infection, and lesion biopsy or cerebrospinal fluid (CSF) examination confirmed the diagnosis. A total of 144 surgical procedures were carried out, including lesion biopsy or excision in 13 patients, primary CSF shunting in 22, and placement of an Ommaya reservoir for administration of intraventricular or intracisternal antifungal agents in 48. All patients received parenteral and, in some cases, intrathecal or oral antifungal chemotherapy in addition to surgical therapy. Overall mortality was 43.6% (34 deaths). With prompt diagnosis and treatment, the mortality rate was 39% whereas, when appropriate treatment was delayed, the mortality rate was 64%. An additional 14 surviving patients (17.9%) exhibited permanent morbidity due to neurological deficits, seizure disorders, or renal toxicity following treatment with amphotericin B. The combined mortality and morbidity rate was 62.8%. Clinical symptoms were resolved completely in 29 patients, although in 10 evidence of disease persisted and chemotherapy was continued. Fungal infections of the CNS are being recognized with increased frequency. It is suggested that a high index of suspicion, aggressive attempts to obtain a diagnosis, and early and vigorous therapy may reduce the unfortunate outcome seen in a relatively high proportion of patients with CNS fungal infections.