The development of non-viral gene therapy has been hampered by an inability to reproducibly manufacture and characterize delivery system components and final formulations. Formation of interpolyelectrolyte complexes as the basis of various gene delivery methods has been approached as the first step towards development of synthetic viruses. We have found that preparation of interpolyelectrolyte complexes from disperse reagents gives a more homogeneous gene delivery vehicle than other methods. Methods which increase homogeneity also result in higher transfection efficiency in vivo. Expression levels of human growth hormone and other reporter proteins in mice confirm the potential of parenteral non-viral gene delivery for some therapeutic applications. Serum is demonstrated to inhibit transfection efficiency in vivo. Our results suggest that further development of methods to manufacture homogeneous disperse non-viral delivery vehicles with stealth characteristics may enhance both the potency and reproducibility of gene transfer in vivo.