Donor failure refers to graft edema present within the first 24 h after penetrating keratoplasty that persists in spite of maximal medical therapy. We reviewed the case histories of 1,351 penetrating keratoplasties. Of these, 17 (1.2%) were considered donor failures. Five cases were histopathologically consistent with Fuchs' dystrophy. Seven cases demonstrated mechanical stripping of the endothelium. Five cases, all from the same eye bank, revealed an absence of posterior stromal keratocytes. Storage medium at the eye bank of origin was found to have an alkaline pH. Careful preoperative evaluation of donor corneas is emphasized, but if an apparent "epidemic" of donor failure occurs, a thorough investigation of the eye bank methodology should be initiated.