Poly (L-lactic acid) -coated polyisobutylcyanoacrylate microcapsules containing protein molecules were prepared by a single-step procedure based on either a double-emulsion-solvent evaporation method or a spray-drying method. First, an aqueous protein solution was emulsified in an organic phase of methylene chloride containing a wall-forming monomer (isobutylcyanoacrylate), various kinds of poly(L-lactic acid), and a surfactant. An immediate polymerization process of isobutylcyanoacrylate takes place at the W/O interface upon contact with hydroxide ion in the aqueous phase, leading to the formation of a polyisobutylcyanoacrylate wall around the aqueous droplets. This W/O emulsion was reemulsified in an aqueous solution to promote the solvent removal and, consequently, the precipitation of poly(L-lactic acid) onto polyisobutylcyanoacrylate microcapsules or was spray-dried to directly deposit the poly (L-lactic acid) on the wall. Three proteins, bovine serum albumin, horseradish peroxidase, and tetanus toxoid, were encapsulated in these poly (L-lactic acid) -coated polyisobutylcyanoacrylate microcapsules, and then their release profiles were examined in vitro as a function of molecular weight of poly(L-lactic acid) and its copolymers with glycolic acid. These formulations exhibited a low "burst" effect at initial incubation stages and released the proteins for extended periods of time. Subcutaneous injections of the tetanus toxoid-loaded microparticles into rats showed that the time course of immunization (antibody titer) can be controlled by the type of polymer matrices used.