The effect of long chain fatty acids on the binding of anti-inflammatory drugs to bovine (BSA) and human serum albumin (HSA) was investigated with the hope that the results obtained would provide some informations about the forces involved in the binding process and the topography of the binding sites on the albumin molecule. The interaction between albumin molecule and oleic and palmitic acids has been investigated at pH 7.4 using Soresnsen's phosphate buffer at 25°C by observing the competition, in binding to proteins, between each acid and either tiaprofenic acid or tenoxicam. By the equilibrium dialysis technique, the capcity of these albumin preparations to bind each tested drug was measured. Analysis of scatchard plots showed that the two drugs occupied two classes of binding sites in both BSA and HSA. The binding of the two drugs to BSA or HSA was inhibited by palmitate or oleate at a molar ratio of either 3.5 or 7. The inhibition affected either the number of binding sites or the association constant for the interaction of the site with the tested drug or both. Binding to either tiaprofenic acid or tenoxicam was markedly reduced, with a significant reduction in number of class 1 sites available. The inhibitory effect of oleate at a molar ratio of 7 on the binding properties of BSA for tiaprofenic acid and tenoxicam was nearly similar to that of 7 mol of palmitate. The binding of the two drugs to HAS containing 7, 3.5 mol of FFA or to HSA free from FFA was less than that observed upon using BSA preparations. These experiments suggest that FFA have a general inhibitory effect on the capacity of albumin to bind tiaprofenic acid or tenoxicam.