The proposed Corneal Transplantation Studies (CTS) consist of two separate yet integrated multicenter double masked clinical studies, a Crossmatch Study and an HLA Matching Study. The purpose of the Crossmatch Study is to determine the efficacy of negative donor-recipient crossmatching in preventing corneal graft rejection in high risk patients with detectable lymphocytotoxic antibodies. Patients will be randomized to receive either a negatively crossmatched cornea or a positively crossmatched cornea. The purpose of the HLA Matching Study is to determine the efficacy of HLA -A, -B donor-recipient matching and HLA-DR donor-recipient matching in preventing corneal graft rejection in high risk patients who do not have detectable lymphocytotoxic antibodies. In this observational study patients will be assigned corneas with different degrees of HLA matching. Both of these double masked studies are organized in essentially the same fashion except for the allocation of donor corneas. Patient surgery and care are the same as for any standard corneal transplant procedure. Patients are required to have frequent and specific eye examinations for the first three post-operative years. The studies will be performed in collaboration with six study centers. Each study center will consist of a clinical center and a tissue typing center working in cooperation with the local eye bank. Procured tissue typed corneas will be shared among the collaborating centers for optimal usage. A Central Tissue Typing lab will manage the distribution of potential recipient bloods and provide quality control assurance among the participating typing centers. Patient data will be collected and sent to a Coordinating center for storage and analysis.