A novel spray-drying technique consisting of feeding a fluid through an ultrasonic atomiser, drying the spray under reduced pressure and collecting the particles in a liquid bath was evaluated. Drying by mild vacuum instead of hot air, as employed in conventional spray-drying, and simple particle recovery render this method suitable for aseptic microsphere preparation. As a model system, the protein bovine serum albumin (BSA) was encapsulated in poly(lactic-co-glycolic acid) microspheres. Particle yields of above 80% exceeded largely values found for conventional laboratory-scale spray-drying equipment. BSA encapsulation efficiency mostly ranged in the region of 60%, with losses probably occurring through partitioning into the aqueous collection bath. Mean particle sizes ranged from 13 to 24 microm, depending on the polymer type and solvent; particle size distributions were excellently reproducible. The microspheres were found to be very porous and exhibited a pronounced 24-h burst release of above 50% of total dose, probably promoted by the porosity. However, when more concentrated polymer solutions (8% instead of 5% (w/w)) were employed, burst release reduced to an average of 16%.