A clinicopathologic study of ten consecutive patients (ten eyes) undergoing surgery for rhegmatogenous retinal detachment with anterior proliferative vitreoretinopathy and a subsequent histopathologic, immunohistochemical, and ultrastructural study of ten enucleated eyes with anterior proliferative vitreoretinopathy were performed in order to elucidate relevant pathogenetic mechanisms. Our findings suggest that the pathogenetic evolution of anterior proliferative vitreoretinopathy occurs in three consecutive stages: (1) traction on the ciliary body and peripheral retina induced by fibrocellular contraction of the vitreous base; (2) incorporation of tractionally denuded components of the ciliary body and peripheral retina into the fibrocellular membranes overlying the vitreous base; and (3) proliferation of the incorporated components and fibrovascular ingrowth from the uvea, the retina, or both, into the fibrocellular membranes. Tractional disruption of the epithelium of the ciliary body pars plicata and breakdown of the ciliary blood-aqueous barrier are the principal pathogenetic mechanisms of chronic intractable hypotony and the post-vitrectomy fibrin syndrome in anterior proliferative vitreoretinopathy.