The pathogenesis of hydrocephalus following reovirus type 1 inoculation of neonatal mice has been examined by light microscopy, radiology, immunofluorescence, and electron microscopy. The reovirus infection causes an acute ependymitis and leptomeningitis, followed by a fibrous arachnoiditis and arachnoid villitis. Hydrocephalus develops in proportion to the degree of inflammatory/fibrotic changes within the cerebrospinal fluid pathways. With the beginning of hydrocephalus there is radiographic evidence of basal cistern blockage. As the hydrocephalic state progresses, axial herniation and compression of the midbrain result in the appearance of aqueduct stenosis. We demonstrate that the stenosis of the aqueduct is a secondary phenomenon, not causally related to the pathogenesis of hydrocephalus, and discuss the significance of this finding to human aqueduct stenosis.