A weak zonular apparatus has been postulated to account for the high incidence of phacodonesis, lens dislocation, and vitreous complications during extracapsular cataract surgery in eyes with pseudoexfoliation syndrome. To clarify and localize the cause of zonular weakness, we examined 11 eyes with pseudoexfoliation syndrome by using scanning and transmission electron microscopy. The production of pseudoexfoliation material by both the nonpigmented ciliary epithelium and the pre-equatorial lens epithelium resulted in typical alterations of the zonules at three levels. (1) At their origin and anchorage in the ciliary body, the zonular bundles were separated from the disrupted basement membrane of the nonpigmented epithelium by intercalating pseudoexfoliation fibers. (2) In the pars plicata of the ciliary body, pseudoexfoliation material infiltrated the zonular bundles passing alongside the ciliary processes leading to zonular rupture. (3) At their attachment to the anterior lens capsule, the zonular lamella was focally lifted and subsequently ruptured by pseudoexfoliation masses erupting through the capsular surface. The immunohistochemical demonstration of lysosomal enzymes within pseudoexfoliation aggregates indicates that proteolytic mechanisms facilitate zonular disintegration. Ophthalmologists treating eyes with pseudoexfoliation syndrome should be aware of these alterations.