The effect of the co-lyophilization of bovine serum albumin (BSA) with poly(ethylene glycol) (PEG) on the BSA encapsulation efficiency and formation of soluble BSA aggregates upon solid-in-oil-in-oil (s/o/o) encapsulation in poly(lactic-co-glycolic) acid (PLGA) microspheres was investigated. Suspension of the lyophilized BSA-PEG formulations in methylene chloride produced small protein powder particles of less than 1 mum diam. and this afforded high encapsulation efficiencies of typically greater than or equal to90% ameliorating one of the problems in s/o/o encapsulation. Formation of soluble BSA aggregates upon s/o/o encapsulation followed by 24 h in vitro release was between 5% and 22%, much lower than values of 59% reported for BSA without stabilizing excipients. Therefore, PEG also afforded BSA stabilization during s/o/o encapsulation. Sustained release occurred over ca. 2 months and was complete.