Comparative studies have been performed on the binding properties of zinc ions to human brain calmodulin and S100b protein. Calmodulin is characterized by two sets of Zn2+ binding sites, with KD ranging from 8.10(-5)M to 3.10(-4)M. The S100b protein also exhibited two sets of zinc binding sites, with a much higher affinity. KD = 10(-7) - 10(-6)M. We suggest that S100b protein should no longer be considered only as a "calcium binding protein" but also as a "zinc binding protein", and that Zn2+ ions are involved in the functions of the S100 proteins.