We describe 2 male patients, a 49-year-old with psoriatic arthritis and impaired renal function and a 43-year-old renal transplant recipient, who both sustained a marked decline in glomerular filtration rate in conjunction with a selective inhibitor of cyclooxygenase-2 (COX-2), rofecoxib. In the second patient, acute renal failure necessitated hemodialysis. Both patients made an uneventful recovery. Our report lends further support to the assumption that COX-2 inhibitors, as a class, can be as nephrotoxic as their nonselective predecessors. Therefore, COX-2 inhibitors should be used with caution in renal transplant recipients and in patients with salt depletion and renal insufficiency.