A method for performing full-thickness, orthotopic, penetrating keratoplasty in the mouse. In an attempt to overcome the lack of well characterized, inbred, and congenic strains, as well as a paucity of immunological reagents, in rabbit and rat models, we have developed a procedure for performing full-thickness, penetrating keratoplasty in the mouse. One hundred percent of isografts (BALB/c onto BALB/c) were successful, while 83.3% of allografts (C3H onto BALB/c) failed. The use of a mouse model to study corneal graft failure will allow a critical evaluation of the role of a variety of immunological mediators in causing graft failure. 