The Collaborative Corneal Transplantation Studies (CCTS) is a set of two multicenter clinical trials designed to investigate the efficacy of donor-recipient human leukocyte antigen matching and crossmatching. High-risk penetrating keratoplasty patients were enrolled through six clinical centers for either the Antigen Matching Study or the Crossmatch Study. All patients were subject to a common set of examinations, treatments, and evaluation procedures. Standard procedures for the identification of high-risk patients, administration of postoperative medications, and recognition and treatment of immunologic allograft reactions were developed and used successfully. These procedures may serve as guidelines for studies in corneal transplantation. Adoption of these methods by other investigators would facilitate evaluation and comparison of results.