The binding of Beta Adrenoceptor antagonist, propranolol and anti-depressant drug, amitriptyline, to bovine serum albumin (BSA) was studied by equilibrium dialysis (ED) method. During concurrent administration, it was found that amitriptyline has the capacity to release propranolol from its binding site on BSA, causing reduced binding of propranolol to BSA. This increment in free concentration of propranolol was from 5.15% to 9.15%, upon the addition of increased concentration of only amitriptyline 0x10-5M to 20x10-5 M, and in the presence of site-II specific probe (diazepam), it was from 6.95% to 10.45%. On the other hand, the release of amitriptyline from the binding sites on BSA was increased from 3.08% to 4.28% upon the addition of increased concentration of only propranolol 0x10-5 M to 20x10-5 M, and in the presence of site-II specific probe (diazepam), it was 0.51% to 4.75%. This form of drug-drug interaction at binding sites on BSA has been termed as site-to-site displacement. Drug-drug interactions, more specifically, displacement interaction will affect the free concentrations drugs in blood. Since the pharmacologic activity of a drug is a function of free drug concentration, the displacement of even a small amount of drug bound to plasma protein could produce considerable increase in activity.