Novel amphiphilic, thermo- and pH-responsive polyaspartamides showing both double-responsive (pH and temperature) behavior and a sol-gel transition were prepared and characterized. The polyaspartamide derivatives were synthesized by the successive aminolysis reactions of polysuccinimide using both hydrophobic N-alkylamine (laurylamine, octylamine, hexylamine) and hydrophilic N-isopropylethylenediamine. The composition of each component was analyzed by H-1 NMR. At the intermediate composition range, the system showed a lower critical solution temperature behavior in water. The transition temperature (pH dependent) could be modulated by changing the alkyl chain length and graft composition. The temperature dependence of the nanoparticle size distribution of the polyaspartamide derivatives was also examined. The critical micelle concentration of the copolymers in a phosphate-buffered saline (pH 7.4) solution ranged from 6 to 20 mu g/L. In addition, physical gelation, i.e., a sol-gel transition, was observed in a concentrated solution. These novel double-responsive and injectable hydrogels have potential biomedical applications such as drug delivery systems and tissue engineering. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 111: 998-1004, 2009