Porcine pancreatic elastase has been used as the model enzyme in the design and development of a crystallographic method that allows mapping of the binding surface of a protein by solving its crystal structure in a variety of organic solvents. The ultimate goal of this method is to aid in the process of drug design, where each of the chosen organic molecules represents a given functional group in a larger inhibitor molecule. This method of multiple solvent crystal structures (MSCS) has a theoretical counterpart in the method of multiply copy simultaneous search (MCSS) (Miranker, A.; Karplus, M. Proteins : Struct., Funct., Genet. 1991, 11, 29-34) and is the first experimental method that can be used as a check to the theory. The MSCS method is presented here with acetonitrile as the probe organic solvent. The procedure involved does not cause significant changes in the structure of elastase as compared to the structure in aqueous solution, and the positions found for the acetonitrile molecules in the active site are compared to those of similar functional groups belonging to known inhibitors bound to elastase.