Mucosal membranes are the most frequent portals of entry of almost all infectious agents. The most important protective humoral factors on mucosal surfaces are locally produced antibodies predominantly of the IgA isotype. Therefore, the induction of specific protective immune responses at mucosal surfaces is a highly desirable goal in the prevention of many infectious diseases. This can be achieved by novel vaccination strategies using effective antigen delivery systems. The ingestion or inhalation of antigens results in the induction of immune responses on mucosal surfaces due to the dissemination of antigen-specific and IgA-committed precursors of plasma cells from intestinal and respiratory lymphoid tissues to other mucosal surfaces. However, only minute quantities of antigens are absorbed from mucosal surfaces due to their degradation by enzymes and hydrochloric acid and inefficient uptake. The protection and enhanced uptake of antigens provided by particles with slow biodegradation could facilitate oral immunization. This possibility has been explored in several recent studies which indicate that simple proteins or complex antigens of viral and bacterial origin incorporated into biodegradable microspheres induce, after ingestion, both mucosal and systemic immune responses. Experimental animals orally immunized with an influenza virus vaccine in biodegradable microspheres displayed virus-specific antibodies in saliva and in serum, and were protected against challenge with the live viruses. Many theoretical and practical advantages of oral over systemic immunization should stimulate further studies of applications of oral vaccines. © 1994.