Zomepirac sodium is a new nonsteroidal anti-inflammatory agent for management of mild to moderate pain. We report five cases of acute renal failure in patients with prior normal renal function. Manifestation of toxic effects has occurred after both short- and long-term exposure and has resulted in varying degrees of azotemia, proteinuria, and oliguria. All patients recovered either with a discontinuance of the drug therapy or with prednisone therapy.