The pharmacokinetics and renal handling of zomepirac, a new analgesic agent, were studied in rhesus monkeys. Single oral 5, 10 and 40 mg/kg doses were administered to fasted male and female rhesus monkeys. After the 40 mg/kg dose, about 2.5-fold higher peak zomepirac plasma concentrations and area under the curve were observed that predicted from the lower doses and plasma clearance decreased from 4.6 to 1.8 ml/min/kg. Because zomepirac is a weak acid and is a substrate for the renal tubular acid transport system, the possible role of concentration-dependent renal clearance was evaluated. Renal clearance of zomepirac averted only 0.007 ml/min/kg and was concentration independent. Essentially all of the plasma clearance was accounted for by formation of the glucuronide conjugate of zomepirac, which was subsequently excreted in the urine. These findings, when placed in perspective with other data, indicate that the nonlinear kinetics of zomepirac in fasted rhesus monkeys are probably due to saturation of metabolism.