To use explants of cornea and iris and ciliary body (I/CB) of experimentally manipulated eyes to determine whether loss of the capacity to suppress T-cell activation in vitro correlates with other consequences of manipulation, ie, the migration of Langerhans cells into the central corneal epithelium, the leakiness of stromal neovessels, and the presence of axons in the cornea. Mouse eyes were subjected to cautery of central corneal surface, suture-induced neovascularization, circumferential or criss-crossed corneal surface wounds, and orthotopic corneal grafting. Corneas and I/CB were excised, explanted in vitro, and assayed for capacity to suppress mixed lymphocyte reaction. Integrity of suture-induced corneal neovessels was assessed with high molecular weight dextran, Langerhans cells were enumerated in corneal epithelium, nerve axons were evaluated in corneal stroma, and capacity of manipulated eyes to support anterior chamber-associated immune deviation (ACAID) induction after anterior chamber injection of bovine serum albumin were assessed. Experimental manipulations that abolished ACAID included cautery, neovascularization, and keratoplasty, whereas criss-crossed corneal excision wounds did not. Loss of ACAID correlated variably with loss of ability of corneal explants to secrete immunosuppressive factors in vitro, presence of Langerhans cells within the central corneal epithelium, leakiness of corneal neovessels, loss of axons in corneal stroma, and loss of ability of I/CB after keratoplasty to secrete immunosuppressive factors. The cornea plays an active role in ocular immune privilege and ACAID by creating a local immunosuppressive microenvironment, providing neural afferent stimuli that affect immunosuppressive properties of I/CB, and preventing neovascularization and infiltration with Langerhans cells.