The influence of a natural protector, the iminoacid proline, on the phase behavior and structure of fully hydrated and freeze-dried dipalmitoylphosphatidylcholine (DPPC) and fully hydrated dihexadecylphosphatidylethanolamine (DHPE) was investigated by differential scanning calorimetry and X-ray diffraction methods. The transition temperatures between the lamellar phases of both iipids increase linearly with proline concentration (2.0, 2.3 and 0.7Β°C/tool proline for the L c --La, --Pa, --L,~ transitions of DPPC, and 3.8 and 0.9Β°C/mol proline for the L c --La --La transitions of DHPE, respectively), while the temperature of the LΒ’, -Hll transition of DHPE decreases linearly by 1.8Β°C/tool of proline. The pre-and main transitions of DPPC merge into a single transition at approx. 3.4 M proline. By extrapolation, the L~ --L~ and L~ --HII transitions in DHPE were found to converge into a direct L~ --H n transition at approx. 5.8 M proline. These data are consistent with a 'kosmotropic' action of proline within the framework of the Hofmeister effect. DPPC dispersions freeze-dried from aqueous solutions of proline display unusual thermotropic behavior, characterized by an endotbermic transition at 71Β°C, followed by a sharp exotherm centered at 76Β°C and a second endothermic transition at 110Β°C. An interpretation, consistent with both calorimetric and X-ray data, is that the endotherm at 71Β°C reflects the melting of a lamellar solid phase into a transient lamellar state with disordered chains which relaxes exothermally at 76Β°C into a new, lamellar solid phase, stable at high temperatures. The latter phase melts, in turn, at 110Β°C, similarly to anhydrous DPPC. In general, this study demonstrates the ability of proline to destabilize the lameilar liquid-crystalline phases in both fully hydrated and freeze-dried lipids.