The elimination kinetics of probenecid in the rat was studied by using an in vitro liver perfusion system to estimate its basic elimination and in vivo to estimate its renal excretion by catheterization of the urinary bladder. In the liver perfusion study different amounts of probenecid were added to the perfusion medium yielding different initial concentrations (40, 200 and 400 μg/ml), and 4 different intravenous bolus doses (50, 75, 100 and 200 mg/kg) were administered in vivo to rats in order to evaluate the renal excretion. The results obtained were described by one-compartment models, with Michaelis-Menten elimination by the liver Vm = 67.4 ± 14.0 (SD) μg/min and a slightly decreasing Km with increasing initial concentrations [from 76.5 ± 9.0 to 53.2 ± (SD) 18.4 μg/ml]. The excretion by the kidney was characterized by a saturable pathway in parallel with first-order elimination, the maximum rate of the active transports Tm = 0.04 ± (SD) 0.09 μg/min, Km,r =100.3 ± (SD) 12.3 μg/ml and a linear renal clearance of 0.0008 ± (SD) 0.0