Suprofen, a nonsteroidal anti-inflammatory drug, has been associated with the onset of acute flank pain, hematuria, and transient renal dysfunction after the ingestion of one or two doses, particularly in young males. Potential mechanisms of this nephropathy were evaluated in normal males following ingestion of suprofen (200 mg) on two occasions: the first with ad libitum fluid intake and the second during forced water diuresis. On the first study occasion, creatinine clearance, the fractional excretions of uric acid (FEUA) and sodium (FENa), the urinary concentration of undissociated uric acid, and the urinary excretions of prostaglandins and glomerular and tubular proteins were assessed. On the second occasion, inulin and PAH clearances and FEUA and FENa were determined. Within 90 min after suprofen administration, the FEUA increased from 8.8 +/- 2.6 to 35.5 +/- 9.6% (p less than 0.05). Urine became supersaturated for uric acid during ad libitum fluid intake. Glomerular filtration rate, renal plasma flow, and FENa decreased significantly, while prostaglandin and protein excretions did not change. The findings are consistent with acute uric acid nephropathy as a mechanism of suprofen-induced renal dysfunction.