The natural binding of inorganic iodide by plasma proteins was studied in 10 freshwater teleost fishes, 16 marine teleost fishes, 3 elasmobranchs, 1 amphibian, 1 reptile, 1 bird, 2 mammals, and 2 arthropods. Of these, significant binding existed only in species of the order Clupeiformes including Esox lucius (average 80.9% of plasma inorganic iodide was protein-bound at 20 C), Coregonus clupeaformis (average 80.3% bound), Salmo gairdneri (average 84.3% bound), and Thymallus arcticus (average 81.0% bound). Significant binding was not found in fish of the orders Cypriniformes, Perciformes, Pleuronectiformes, Batrachoidiformes, Gadiformes, Squaliformes, Chimaeriformes, and Rajiformes. Esox lucius and C. clupeaformis showed a small seasonal variation in binding capacity. The plasma of male fish bound significantly more iodide than did the plasma of female fish.Inorganic iodide was found to bind with a plasma albumin-like protein. The binding sites were presumably free cationic groups of basic amino acid residues on the protein molecules. Iodide binding was inhibited by NO3−, SCN−, ClO4−, and CCl3COO−, but not affected by thiourea, thiouracil, and other halide ions. Binding energy was weak in both E. lucius (−5.98 Kcal/mole) and C. clupeaformis (−6.08 Kcal/mole).