The effect on lung accumulation of modifying the surface compositions of 9 9 m Tc poly(lactide-co-glycolide) (PLGA) and 9 9 m Tc poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) microspheres with different surfactants was assessed after intravenous injection into rats. Microspheres were prepared with PLGA or PEG-PLGA by the emulsion solvent evaporation method using polyvinyl alcohol (PVA), polyethylene glycol (PEG), albumin (BSA) or poloxamer 188 as surfactant, in the external aqueous phase. Commercial human albumin microspheres (Sferotec ( R), HAM) were used as reference. According to the European Pharmacopeia, >80% of 9 9 m Tc-HAM in the size range 10-50 μm, must be accumulated in the lung 15 min after intravenous administration. By modifying the surfactant, the resulting lung accumulation was 99% for 9 9 m Tc-HAM, and more than 50% for PLGA microspheres prepared with poloxamer 188 (1 and 4%), reaching 67% with 8% Poloxamer 188 and around 30-39% for PLGA and PEG-PLGA microspheres prepared with the other surfactants. PLGA microspheres made with 8% poloxamer 188 gave good quality lung images under a gamma camera for the first few minutes, subsequently liver radioactivity masked lung images.