The prevailing hypothesis concerning the pathogenesis of toxoplasmic hydrocephalus alleges that (a) parasites invade and destroy the ependymal lining of the lateral ventricles, followed by (b) the sloughing of masses of degenerating ependymal and inflammatory cells leading to obstruction of the ventricular foramina and aqueduct of Sylvius, thereby initiating the hydrocephalus. Our observations in chronically infected mice indicate otherwise. Parasite invasion of the ependyma was not detected; the intraventricular masses of cellular ‘debris’ contained neither ependymal nor inflammatory cells; and obstruction of the ventricular foramina and/or aqueduct was not seen. As an alternative hypothesis, we suggest the development of hydrocephalus in the infected mice was consequent to severe leptomeningeal inflammation blocking the subarachnoid space and impeding the resorption of cerebrospinal fluid by the arachnoid villi. Narrowing of the aqueduct of Sylvius, when present, was adjudged the result, not the cause of the hydrocephalus, due to compression of the midbrain by the enlarging lateral ventricles.