Three patients experienced rapidly reversible azotemia related to the use of naproxen or ibuprofen but tolerated full-dose sulindac. This article discusses renal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs), with emphasis on the role of inhibition of prostaglandin synthesis, and reviews evidence supporting a renal-sparing property of sulindac. The current literature assumes that all NSAIDs possess a similar potential for renal toxicity. The data presented suggest that sulindac has less potential for renal toxicity and may be the preferred NSAID for use in patients with impaired renal function.