A new method is presented for calculating a type of quantitative structure-activity relationship, given experimental data on the binding affinity of a series of ligands to a receptor site on a protein. All ligands are presumed to have known chemical structure but may be conformationally flexible, and all are presumed to bind to the same, single, fairly rigid site of the (pure) receptor protein molecule. Given the experimentally determined free energies of binding of the ligand molecules, possible binding sites are deduced in terms of geometry and the chemical character of the various parts of the site. A test of the method is given for a series of chymotrypsin inhibitors and for a series of dihydrofolate reductase inhibitors. The proposed dihydrofolate reductase site suggests that a quinazoline inhibitor may rock between two different binding nodes depending on the pK of the ring N(1).