The purpose of this study was to identify new trends in the changing indications for penetrating keratoplasty. We retrospectively reviewed the clinical and pathologic diagnoses of 1,104 corneal buttons that had been submitted to the Estelle Doheny Eye Pathology Laboratory, Los Angeles, during the 5-year period 1989–1993. The leading indications, in order of decreasing frequency, were pseudophakic corneal edema (24.8%), regrafts (21.3%), scarring with or without chronic inflammation (11.1%), keratoconus (7.1%), aphakic corneal edema (6.4%), and ulcerative conditions (5.8%). The incidence of pseudophakic corneal edema remained stable over the study period and was actually surpassed by regraft in the last year of the study. Although pseudophakic corneal edema remains the predominant indication for penetrating keratoplasty, our findings suggest that its occurrence rate has begun to level off.