In a transmission electron microscopic investigation of the endothelium lining Schlemm's canal subjected to graded levels of intraocular pressure (0 to 50 mm Hg for one hour), there was an increase in the number of vacuolar structures with the increase in pressure (range, 8 to 30 mm Hg). At 0 mm Hg, giant vacuoles were absent, while at 50 mm Hg their numbers were less than at 22 and 30 mm Hg. Vacuoles were invaginations either from the meshwork or from the canal surface of the endothelium. A few were transcellular channels that possibly served as a pressure-sensitive outflow system. In addition, the numbers of nonvacuolar transcellular channels and minipores increased with an increase in pressure while the numbers of pinocytotic and micropinocytotic vesicles decreased. The changes were not accompanied by alterations in organelles associated either with protein or energy production. At 50 mm Hg, breaches in the endothelium lining the trabecular wall were obvious and aqueous outflow was considered to be by nonphysiologic routes.