Primary angiitis of the central nervous system (PACNS) is a rare form of angiitis limited to the central nervous system. The diagnosis and classification of this disorder has been problematic, owing to the lack of uniform diagnostic criteria and the difficulty in obtaining pathologic material for diagnosis. This study proposes to establish diagnostic criteria for PACNS which would include 1) the presence of an unexplained neurologic deficit after thorough clinical and laboratory evaluation; 2) documentation by cerebral angiography and/or tissue examination of an arteritic process within the central nervous system; and 3) no evidence of a systemic vasculitide or any other condition to which the angiographic or pathologic features could be secondary. Utilizing these criteria, 8 new cases are reported and are combined with 40 previously diagnosed cases from the literature. The clinical findings of the combined series revealed that headache was the most common symptom (58%) with a combination of focal and diffuse neurologic deficits described in 79% of the group. The diagnostic approach to PACNS should include a variety of laboratory tests and examination of the cerebral spinal fluid primarily to rule out mimicking conditions. Special procedures including electroencephalography, computed axial tomography, and magnetic resonance imaging appear only marginally helpful in securing the diagnosis, but are extremely important in ruling out other conditions. Angiography appears to be the first invasive diagnostic procedure of choice and it has a high predictive value when properly interpreted. Leptomeningeal and cortical biopsy can be accomplished with acceptable mortality and should be performed along with a normal or non-diagnostic angiogram when the diagnostic likelihood is high. Therapy of PACNS with a combination of cytotoxic drugs and high-dose corticosteroids has greatly improved the prognosis for this condition.