Our new hypothesis for the regulation of aqueous humor outflow suggests that the trabecular meshwork is not a passive filter but an active contractile element contributing to the ciliary muscle traction affecting it. The trabecular meshwork contains contractile smooth-muscle-specific α-actin filaments, and its cells exhibit electrical properties typical for smooth muscle cells. Contractility measurements performed for the first time in isolated trabecular meshwork enable a functional comparison with ciliary muscle. Pharmacologic outflow regulation has been determined in isolated perfused anterior segments with intact trabecular meshwork and total absence of ciliary muscle. Substances that contracted isolated trabecular meshwork (eg, pilocarpine) decreased the outflow rate, whereas relaxants (eg, low-dose epinephrine) increased it. The concept of a functional antagonism between the trabecular meshwork and the ciliary muscle has to be considered.