The interaction of metal cations with single chain glcbular proteins produces volume increases, the magnitude of which is determined primarily by the ion and to a lesser extent by the protein. The cations are listed in ascending order of volume change: K(I) < Mg(II) < Sr(l1) < Ca(I1) < Co(II) < Ni(II) < Cd(R) < Zn(II) < Cu(II) < Pb(I1). This sequence held for all cation-protein systems investigated except for Cd(H) which produced a slightly larger volume effect than Zn(I1) with lysozyme. The volume changes attributed to protein-cation interaction are positive and range from 8 ml/lo' g of protein for the reaction on 0.05 M KNO, with bovine plasma albumin to 2320 ml/lo5 8 of protein produced by the 0.20 M Pb(NO,),-myoglobin system. A similar classification scheme was not possible for the proteins. For example, volume increases of 4.5, 50, 80 and 95 ml/lo5 g of protein were produced when 0.05 M Mg(II) reacted with bovine serum albumin, ovalbumin, sperm whale myohlobin and lysozyme, respectively. However, when 0.2 M Pb(II) was the reactant the values were 1930, 846, 2320, and 1120 ml/LOS g of protein Volume effects produced by Cr(III), Al(III) and Fe(lII) were determined, but the calculated results are considered dubious because the volume changes are a complicated function of proteincation and proteirrproton interaction