We observed elevation of serum creatinine and blood urea nitrogen and decrease in creatinine clearance in patients taking anti-inflammatory doses of aspirin. In 13 of 23 patients with systemic lupus erythematosus increases in serum creatinine ranged from 27 to 163 per cent, and those in urea nitrogen from 42 to 270 per cent. Sequential creatinine-clearance studies, available in 11 of the 13 patients, demonstrated decreases up to 58 per cent. Patients with aspirin-induced changes in renal function were more likely to have active renal disease (P = 0.035) or hypocomplementemia (P = 0.030). Four of 22 patients with rheumatoid arthritis and two of three normal volunteers also demonstrated biochemical changes. The rate of aspirin-induced alterations was significantly higher in systemic lupus erythematosus (P = 0.007) than in rheumatoid arthritis. Aspirin, and other nonsteroidal anti-inflammatory agents, can have a major reversible effect on renal function that may influence the interpretation of clinical data. (N Engl J Med 296:418–424, 1977) Effects of aspirin on the kidney, although recognized for at least 60 years, rarely pose problems in the clinical management of patients. Changes in body water,12 urinary shedding of cells,3456 changes in glomerular78 and tubular9 function and the possible role of salicylates in analgesic nephropathy1011 have been studied. Interest has also focused on the ability of the drug to inhibit prostaglandin synthesis121314 as a potential mechanism for the modulation of certain renal effects.1516 Therapeutic problems, however, rarely arise from these changes. Recently, we have noted striking effects of therapeutic doses of aspirin17 on renal function in patients undergoing evaluation of. © 1977, Massachusetts Medical Society. All rights reserved.