Certain drugs with metabolism that obeys Michaelis-Menten kinetics are extensively bound in the liver. During the initial distribution phase after a single dose, the binding sites act as a "sink" and compete with the metabolizing enzymes for the drug. After this phase is completed, the bound sites act as a source of drug for the enzymes. Computer simulations of a perfused liver system, with well-stirred reservoir and hepatic compartments, were performed to assess whether or not such binding, as measured by the partition coefficient (Kp) between the liver and the emergent venous blood, affects the tendency to saturate metabolism. Metabolism was assumed to follow Michaelis-Menten kinetics and only unbound drug was assumed to have access to the enzymes. The value of Kp was varied to determine the effect of binding (instantaneous equilibrium) on the tendency to saturate metabolism. The effect of binding rate was also determined by adjusting the association and dissociation rate constants while maintaining a constant value of the equilibrium partition coefficient. Input into reservoir and liver were done to simulate "intravenous" and "oral" dosing, respectively. The average clearance (dose divided by the area under the reservoir concentration-time curve) of the "intravenous" dose increased and the bioavailability of the "oral" dose decreased when the value of Kp was increased, indicating that the tendency to saturate metabolism was reduced by hepatic binding. This effect diminished as the binding rate constants were made smaller, but was still substantial, when association was slower than metabolism.