The incidence of potentially serious drug-related elevations of BUN or serum creatinine was examined among 1468 patients with rheumatoid arthritis or osteoarthritis who took daily therapeutic doses of aspirin, ibuprofen, or oxaprozin, an investigational nonsteroidal antiinflammatory drug (NSAID), in multicenter clinical trials. Algorithms were developed to identify patients with potentially important elevations of these renal laboratory parameters and to assess the possible relation between these elevations and the study drugs. All three drugs were associated with a low (4% to 6%) incidence of potentially significant elevations in renal function parameters. Changes considered serious occurred in only three (less than 1%) patients (one treated with oxaprozin and two with ibuprofen), all of whom were receiving concomitant diuretic therapy. None of the changes led to adverse clinical consequences. Thus despite recent controversy regarding the renal safety of NSAIDs, all three drugs proved safe in these studies, despite the fact that aspirin and ibuprofen were given in doses equal to or higher than those used for over-the-counter indications.