Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, suppress renal prostaglandins and markedly reduce renal perfusion and diuretic response in some renal disorders. Mild renal impairment may occur in healthy subjects. Pharmacodynamic characteristics of certain NSAIDs, such as the nonacetylated salicylates, suggest that they may have less deleterious renal effects. We compared the renal effects of standard therapeutic doses of indomethacin, ibuprofen, aspirin, and the nonacetylated salicylate, diflunisal, in 6 healthy supine volunteers. Only indomethacin significantly reduced creatinine clearance (by 13%) and renal plasma flow (by 23%; p less than 0.05). Indomethacin also tended to reduce furosemide-induced diuresis and natriuresis, and this effect was significantly greater than with diflunisal (p less than 0.05). Serum thromboxane, a reflection of platelet cyclo-oxygenase activity, was reduced by 99% with aspirin, ibuprofen and indomethacin, but by only 78% with diflunisal. Nonacetylated salicylates may be the preferred drugs, at least in short-term usage, when it is necessary to minimize the effects of NSAIDs on platelet or kidney function.