Poly(ethylenc, glycol)-grafted-poly(amido amine) (PEGylated-PAMAM) dendrimers have attracted increasing amounts of attention because of their improved stability, toxicity, and better particle drug leakage property. The complexation of alpha-cyclodextrin (alpha-CD) with grafted PEG segments on the surface of PAMAM dendrimers was elucidated by light scattering and titration calorimetry. At pH 10, complexation between alpha-CD and PEGylated-PAMAM occutred once alpha-CD was titrated into the PAMAM solution. We observed for the first time a unique phenomenon at pH 2, where no binding took place until a critical alpha-CD concentration (C*) of similar to 8.0 mM was reached. The size of the rianostructures increased from 6.7 to 57.6 nm when the alpha-CD concentration was increased from 0.5 to 15 mM at pH 2. The zeta potential of PEGylated-PAMAM at pH 2 was +6.7 mV. Thus, the dendrimers possessed positive charges attributed to the protonation of primary amine groups on PAMAM chains that impart electrostatic repulsive forces to the system. The morphology of the complex is expected to be different at two different pH values (2 and 10) because the former produces a clear solution and the latter forms a turbid solution with white precipitates.