Poly(d,l-lactic acid) (PLA) nanoparticles were prepared by a modified emulsification-diffusion technique. The preparation method consisted of emulsifying a solution of polymer in an aqueous solution of a stabilizing agent, previously saturated, followed by diluting the internal phase with an excess of water. Propylene carbonate (PC) was used as a partially water-miscible solvent, due to its ability to dissolve polymers, its low toxicity and its ease of emulsification. PC allowed the obtention of nanospheres in a reproducible and efficient way, using poly(vinyl alcohol) or poloxamer 188 as stabilizing agents. The possibility of using poloxamer 188 to produce PLA nanospheres is an interesting option because of its well known acceptability for parenteral administration. With other well accepted stabilizing agents such as polysorbate 80, gelatin, polyvinylpyrrolidone and dextran, it was not possible to obtain nanoparticles. The effectiveness of the stabilizing agents in the process was attributed to their ability to avoid coalescence during PC diffusion. The formation mechanism of nanoparticles can be explained by the large interfacial area resulting from emulsification and the gradual reduction of the globule size due to solvent transfer and probably, to the interfacial turbulence generated during diffusion. A higher concentration of polymer was found to rapidly increase the size and polydispersity of nanoparticles. In contrast, an increase in stirring rate and concentration of stabilizer agent were found to reduce moderately the size of the nanoparticles. Other process parameters such as viscosity, pH of the external phase and internal/external phase ratio had limited influence on particle size.