Nanoparticles for drug delivery and other industrial uses have been prepared by sonicating poly-L-lysine graft copolymer amphiphiles in aqueous media. These nanoparticles are able to entrap hydrophilic molecules. Graft copolymers, which have a poly-L-lysine backbone, varied levels of hydrophilic methoxypoly(ethylene glycol), and hydrophobic palmitoyl pendant groups, were prepared by reacting methoxypoly(ethylene glycol)p-nitrophenol carbonate (M-r = 5000) followed by palmitic acid N-hydroxysuccinimide ester with two different molecular weight poly-L-lysine hydrobromide samples (similar to 4000 and similar to 20 000, respectively). These amphiphilic polymers (PLP) were characterized using light scattering, H-1 NMR, and an assay for the level of free amino groups. Steric factors seem to limit the final level of lysine group modification that can be achieved, and even an excess amount of grafting reactants (mole ratio of L-lysine to grafting reactants = 0.63) still resulted in the production of polymers in which 22-26 mol % of the lysine epsilon-amino groups remain unsubstituted. Probe sonication of an aqueous dispersion of PLP samples resulted in the production of stable colloidal dispersions (80-170 nm in diameter). Nanoparticle size was influenced by the initial poly-L-lysine molecular weights. Poly-L-lysine of M-r similar to 4000 and M-r similar to 20 000 resulted in PLP graft copolymers with molecular weights of 32 000-48 000 and 89 000-140 000, respectively, and ultimately nanoparticles of 85-114 nm and 125-167 nm in diameter, respectively. An increase in the level of unreacted amino groups increased the level of encapsulation of the hydrophilic fluorophore fluorescein isothiocyanate (FITC)-dextran (M-r = 4400). Amphiphilic polymers of molecular weight 89 000 or 140 000 and possessing either 42 or 27 mol % unreacted poly-L-lysine units, respectively, encapsulated 3.8 +/- 0.5 and 1.8 +/- 0.4 wt % FITC-dextran, respectively. This work demonstrates that stable nanoparticles may be prepared by the one-step probe sonication of an amphiphilic poly-L-lysine graft copolymer and also that the molecular architecture and molecular weight of this new series of amphiphiles influence the size and hydrophilic loading of the resulting nanoparticle dispersion.