Subdural empyema is an intracranial infection that has remained difficult to diagnose and to treat. Seventeen patients with this infection, treated between 1967 and 1974, are analyzed and compared to published series with particular regard to diagnosis using newer procedures and treatment, considering the primary focus of infection. The infection is usually located in the supratentorial spaces, is often bilateral, and results most often from para-nasal sinusitis (single most common cause), otitis, neurosurgical operative infections, and meningitis in infants. Patients suffering from subdural empyema generally present with rapid onset of depressed sensorium, seizures, focal neurological deficits, and signs of increased intracranial pressure, following a period of days to weeks characterized by headache and fever. All 17 of our patients demonstrated localizing neurological signs and 16 manifested either fever or leukocytosis. Diagnostic studies, except for cerebral arteriography, do not reliably corroborate or exclude the diagnosis. Cerebral arteriography established the diagnosis and defined the location and extent of the empyema in all of our cases. The EEG and brain scan produced frequent false-negative and/or non-localizing results in 10 and 8 patients, respectively. The cerebrospinal fluid was abnormal from all 15 patients examined by lumbar puncture, but the findings were similar to those in other infectious and non-infectious central nervous system diseases. Signs of transtentorial herniation developed within eight hours following lumbar puncture in three of seven patients who had exhibited signs of increased intracranial pressure before the procedure was performed. Bacterial cultures were positive in 13 of our cases. A review of our data and that of other studies indicates that the organisms associated with subdural empyema are consistent with those expected from infections of the primary site; e.g. sinusitis, otitis, meningitis, site of prior neurosurgery. A therapeutic approach is suggested which emphasizes specific antibiotic regimens appropriate to the primary site of infection and prompt neurosurgical intervention with evacuation of the subdural spaces bilaterally. In general, combination antimicrobial therapy employing high parenteral doses of penicillin G, a semi-synthetic penicillinase-resistant penicillin and chloramphenicol is recommended.