Effects of renal disease on the disposition kinetics of oxaprozin, a nonsteroidal antiinflammatory analgesic, were assessed in 15 subjects who were normal, renally impaired or who had been undergoing hemodialysis. Oral dose clearance (Cloral), volume of distribution at steady-state (Vssd) and elimination half-life (t1/2) did not substantially differ among the 3 groups. Mean fraction unbound oxaprozin in plasma (fup) increased from 0.08% in the normal group to 0.18 and 0.28% in the 2 azotemic groups. Unbound drug kinetic parameters, including intrinsic clearance (Clint) and Vssdu of unbound drug were reduced from 2.9 l/h per kg and 193 l/kg in normal subjects to .apprx. 1.6 l/h per kg and 91 l/kg in azotemic patients. The smaller volume of distribution is consistent with a decrease in oxaprozin tissue binding in azotemia. The decreased plasma and tissue binding and lower Clint suggest that, in the treatment of azotemic patients with rheumatoid arthritis, the dose of oxaprozin should begin at 600 mg once a day.