Using differential scanning calorimetry the thermotropic behaviour of the acidic phospholipid dipalmitoylphosphatidylglycerol (DPPG) was studied as a function of pH, concentration of NaCI and the concentration of organic polyvalent cations, polyamines. Although changes in hydration forces and hydrophobic effect may be involved the measured pH/[NaC1]/T m phase diagram for DPPG suggests that, even at pH 8.5, DPPG is incompletely deprotonated. In terms of energetics however, the observed changes of about IΒ°C are relatively minor corresponding to a bilayer free energy change of 30 cal/mol. The effects of spermine and spermidine on the phase transition of DPPG were strongly concentration dependent even in the micromolar range. The observed effects correlated to the number of positive charges in these cations and thus the greatest effect was observed for spermine. Specific and nonspecffic interactions between DPPG and spermine are suggested to exist which are both reversed by high concentrations of NaCI. These results indicate that under proper conditions changes in the intracellular concentrations of polyamines may be capable of triggering an isothermal phase change in membrane acidic phospholipids.