We demonstrate a simple and successful synthetic approach to devise a highly efficient DNA delivery system with low cytotoxicity and low cost. Polyamidoamine (PAMAM) dendrimer is a highly efficient DNA delivery agent, when compared to other chemical transfection reagents. Partially degraded, high-generation dendrimers offer even higher efficiency, presumably due to enhanced flexibility of the otherwise rigid dendrimer chains.' We hypothesized that chemical modification of low generation dendrimer with biocompatible poly(ethylene glycol) (PEG) chains would create a conjugate of PAMAM core with flexible PEG chains, which mimics the fractured high-generation dendrimer and produces high transfection efficiency. Generation 5 PAMAM was modified with 3400 molecular weight PEG. The novel conjugate produced a 20-fold increase in transfection efficiency compared with partially degraded dendrimer controls. The cytotoxicity of PEGylated dendrimers was very low. This extremely efficient, highly biocompatible, low-cost DNA delivery system can be readily used in basic research laboratories and may find future clinical applications.