Proteins associated with metals serve many important biological functions. The amino acid residues provide the functional groups in a protein which are the potential ligands for a metallic cation. Metals impart various effects on protein structure and bring about overall structural stability. These effects are seen in quarternary, secondary and tertiary structures of the protein. There are varieties of approaches to study metal protein interactions. The earliest technique being the equilibrium dialysis which is still used extensibly to determine the binding strength and the number of metals bound per protein molecule. There are a number of other techniques available which provide precise information about the nature of metal binding sites. They include electron spin resonance, UV and visible spectoscopy, nuclear magnetic resonance, resonance Raman, X-ray crystallography, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (XAFS), etc. Selected metal protein interactions are discussed in this review. Albumin is the major plasma protein in blood which transports a number of metals. Detailed studies of Cu(II) and Ni(II) binding to albumin suggests that both metals have the same specific binding site at the NH2-terminal tripeptide sequence (Asp1-Ala2-His3...) involving the Asp alpha-NH2, His3 N (1) imidazole, two deprotonated peptide nitrogens (Ala2NH and His3NH), and Asp1 COO- group. Transferrin transports Fe(III) in blood. The protein possesses two metal-binding sites, each within a domain of bilobal proteins. Presence of carbonate is an important feature of Fe(III)-binding to transferrin. The binding site has been postulated as one involving Tyr 185 and Tyr 188 and suggests that two of the three histidines His 119, His 207 and His 249 also serve as ligands. Arginine 145 is a likely anchor for the carbonate anion. Superoxide dismutase is an enzyme found in erythrocytes which catalyzes the dismutation of superoxide radical. The protein is a dimer made up of two equivalent subunits. The subunits are held together by noncovalent interactions. For optimal enzymatic activity, at least two of the protein's four metal ions must be cupric. The results of the X-ray crystal structural analysis for Cu(II) and Zn(II) containing protein have been reported. In the metal-binding region of one subunit, Cu(II) and Zn(II) are separated by approximately 6A. The Cu(II) is bound to imidazole side chains of histidines 44, 46, 61 and 118 in a distorted square planar arrangement. The imidazole ring of histidine 61 is believed to be deprotonated and to serve as a bridge between Cu(II) and Zn(II).(ABSTRACT TRUNCATED AT 400 WORDS)