Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber in surgically virgin, aniridic, and ciliary muscle disinserted cynomolgus monkey eyes 6 to 13 times at 1- to 2-month intervals over periods of 8 to 24 months. Facility decreased approximately 15 to 20% between consecutive thirds of the perfusion history, independent of eye type. The facility decreases were too large to be explained by decreased uveoscleral facility or pseudofacility, and were not mediated by the iris, ciliary muscle, or gonioscopically or ultrastructurally apparent chamber angle alterations. They most probably reflected functional alterations in the trabecular meshwork/inner wall of Schlemm's canal. Intraocular pressure as measured by applanation tonometry did not increase progressively, most probably due to a decreased rate of aqueous humor formation.