Complex nanoparticle formation of poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL) block copolymers with ribozyme (Rzs) in an aqueous solution was studied. Nanoparticles formed from PEG-b-PLL and Rzs have about 100 nm in an effective diameter with the hydrophilic PEG segments stabilizing and surrounding the core of complexes formed between the PLL segments and Rzs. The block copolymer having a higher positive charge formed relatively smaller complex nanoparticles. The profile of the ethidum bromide (EtBr) displacement assay and images of agarose gel electrophoresis revealed the condensation of Rzs to form complex nanoparticles above a critical weight ratio, r (r: 4.0 for PEG(5000)-b-PLL1920 and 3.0 for PEG(5000)-b-PLL3840). Furthermore, the PEG-b-PLL/Rz complex nanoparticle showed high resistance against RNase attack in biological fluids.