OBJECTIVE AND IMPORTANCEWe describe two patients with symptomatic septum pellucidum cysts managed by endoscopic fenestration. In each case, tissue from the cyst wall was studied to define the origin of the cyst wall and fluid.CLINICAL PRESENTATIONThe patients, a 6-year-old boy and a 42-year-old man, each presented with headaches and a syncopal episode. Imaging studies demonstrated large septum pellucidum cysts with obstruction of the foramina of Monro.INTERVENTIONThe patients underwent endoscopic transventricular cyst fenestration with a 4-mm steerable fiberscope. The fenestrations were created to allow communication with the right and left lateral ventricles. In one patient, adhesions between the cyst wall and the foramen of Monro were lysed with endoscopic monopolar cautery. Tissue from the cyst walls was removed for examination by electron microscopy. Postoperatively, the headaches and syncopal episodes resolved in both patients.CONCLUSIONEndoscopic fenestration of symptomatic septum pellucidum cysts produces immediate relief of the mass effect of the cyst and resolution of associated symptoms. Cannulation of the lateral ventricle before cyst fenestration prevents inadvertent injury to the fornices, thalamus, internal capsule, caudate nucleus, and septal and thalamostriate veins. The endoscopic approach allows the surgeon to ensure communication within the ventricular system, thus avoiding placement of a shunt. Preliminary ultrastructural analysis indicates that the cyst walls derive from the septum pellucidum rather than the choroid plexus or arachnoid. The cellular machinery necessary for fluid secretion was identified in some specimens.