From three groups of patients with corneal edema, the degree of edema was clinically quantified prior to penetrating keratoplasty. Corneas from patients with failed grafts (n = 16) had the greatest edema (mean score 3.8 +/- 0.6 SE), corneas with Fuchs' endothelial dystrophy (n = 12) had the least edema (1.4 +/- 0.4), and corneas with aphakic and pseudophakic bullous keratopathy (n = 40) had intermediate edema (2.7 +/- 0.5). Phosphorus-31 nuclear magnetic resonance spectroscopy was used to quantitate five high-energy phosphates and nine low-energy phosphates and calculate 12 metabolic indices from the specimens of these three edematous groups. Corneas with aphakic and pseudophakic bullous keratopathy had lower alpha-glycerophosphate (alpha-GP) and glycerol 3-phosphorylethanolamine and glycerol 3-phosphorylcholine (GPE & GPC), and higher phosphocreatine (PCr), adenosine diphosphate (ADP), monoesters/diesters, PCr/Pi (phosphocreatine/inorganic orthophosphate), and PCr/ATP (phosphocreatine/adenosine triphosphate) than corneas with Fuchs' endothelial dystrophy (p less than 0.05). Corneas from failed grafts had lower alpha-GP, ethanolamine phosphate (EP), ethanolamine phosphate and choline phosphate (EP&CP), monoesters/Pi, ATP/Pi, and energy modulus, no detectable GPE and GPC, and higher Pi, phosphorylglycans (PG), PCr, ADP, diesters, PCr/Pi, and PCr/ATP than those with Fuchs' endothelial dystrophy (p less than 0.05). Corneas from failed grafts had lower ATP, monoesters/Pi, ATP/Pi, PCr/Pi, and energy modulus and higher Pi, PG, ADP, diesters, and PCr/ATP than corneas with aphakic and pseudophakic bullous keratopathy (p less than 0.05). In summary, there was increasing decline in the high-energy metabolites and energy status with increasing edema.