Biodegradable poly(DL-lactic acid) nanoparticles (NP) produced by the salting-out process were evaluated in vitro and in vivo for their sustained release properties and their capacity to temporarily avoid the mononuclear phagocyte system (MPS). In vivo, NP loaded with neuroleptic compound savoxepine were able to provide sustained plasma levels after intramuscular and intravenous injection. Intramuscularly injected NP were successfully coated during the preparation procedure with PEG 6000 and PEG 20 000. In vitro, these coatings provided a protective barrier against extensive uptake by human monocytes, at least in plasma. Analysis of plasma proteins absorbed on NP and in vitro experiments on isolated cells revealed some differences between the opsonization process of plain and coated NP. Plain and PEG 20 000-coated NP loaded with photosensitizer hexafluoro zinc phthalocyanine were injected intravenously to mice bearing EMT-6 mouse mammary tumors. The protective coating produced a dramatic increase of the photosensitizer concentration in blood and tumor as well as a decrease in the MPS sequestration. These findings suggest that surface-modified NP should prove useful for the delivery of chemotherapeutic drugs to tumoral tissues.