A variety of physical and chemical methods are being used to investigate configurational changes in proteins which result from limited proteolysis, disulfide interchange, ligand binding, protein-protein associations, and minor changes in amino acid sequences. The products of limited proteolysis of bovine plasma albumin preparations by endogenous contaminant proteinases are being characterized. The goals are to establish whether the cleavage pattern is different under different conditions of digestion and to determine whether different proteinases are responsible for the cleavages. We have evidence that the A isomer of bovine plasma albumin differs from the native protein by a shuffled disulfide bridge. Attempts are being made to characterize differences in the conformation of native and A isomer plasma albumin by means of 19F and 13C nmr spectroscopy. Proton nmr spectroscopy is being used to study the histidine residues of the ribonuclease A dimers of Crestfield and of ribonuclease T1. Assignments of nmr peaks to individual residues are underway. Amino acid sequencing techniques are being used to investigate differences in members of the glutathione S-transferase class of enzymes and an amino acid replacement of quail ovomucoid.