The disposition of diflunisal was studied at daily doses of 250, 500, 750, 1000 mg/day in 24 male patients (mean age 65 yr and mean creatinine clearance 72 ml/min). Each dose was given for 14 days and diflunisal apparent oral clearance and serum urate was measured on the last day of each dosing regimen. There was a dose-dependent decrease in mean diflunisal apparent oral clearance with dose from 628 ml/hr at 250 mg/day to 426 ml/hr at 1000 mg/day, with most of the decrease occurring at the lower doses and becoming less pronounced at doses of 750 and 1000 mg/day. There was a strong positive correlation between diflunisal apparent oral clearance and creatinine clearance. Diflunisal induced a hypouricemic effect at all doses, but the responses at doses of 750 and 1000 mg/day did not differ.