Isothermal titration calorimetry was used to experimentally determine thermodynamic values for the ethylenediaminetetraacetic acid (EDTA)(aq) + M[superscript 2+](aq) reactions (M[superscript 2+] = Ca[superscript 2+] and Mg[superscript 2+]). Students showed that for reactions in a N-(2-hydroxyethyl)piperazine-N"-ethanesulfonic acid (HEPES) buffer (pH = 7.4), the Mg[superscript 2+] + EDTA reaction was endothermic, while Ca[superscript 2+] binding to EDTA was exothermic. EDTA is triply ionized at pH 7.4 and therefore must shed a proton to the buffer prior to chelating the M[superscript 2+] ion; thus the observed reaction enthalpies are strongly dependent on pH and buffer ionization enthalpy.