We conducted a prospective study in 114 elderly patients to determine the renal effects of short-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) in the very old. Study subjects were patients in a long-term care facility (mean age, 87 years) newly begun on a regimen of NSAID therapy. For the study group as a whole, the serum urea nitrogen level rose 1.7 mmol/L 5 to 7 days after initiation of therapy, with no significant changes in serum creatinine or potassium levels. In a comparison group of 45 patients not receiving NSAID therapy, no significant change in the serum urea nitrogen level was noted during a similar period. A subgroup of 15 patients (13%) experienced a greater than 50% increase in the serum urea nitrogen level during NSAID therapy, with a mean increase of 89% (8.6 mmol/L). A return to the baseline level occurred within 14 days after discontinuation of NSAID therapy. Two factors were significant predictors of a greater than 50% increase in the serum urea nitrogen level: concurrent loop diuretic therapy (odds ratio, 2.2) and high NSAID dose (odds ratio, 2.0). These findings suggest that reversible azotemia develops in a sizable proportion of the very old who are treated with short-term NSAID therapy.