The effects of different amounts of four natural polyamines on the thermodynamics of the thermal denaturation of calf thymus and herring sperm DNA have been studied by means of differential scanning calorimetry. Enthalpy changes and the temperature of the maximum heat effect were determined. The stability of the double helix increases by increasing the polyamine/phosphate ratio and the number of positively charged groups on the polyamine molecule. A combination of Manning’s polyelectrolyte theory and McGhee and von Hippel’s multiple-site exclusion approach has been demonstrated to give a very good reproducibility of experimental results.