Microencapsulated Fl and V sub-unit antigens of Yersinia pestis were used to immunize mice intraperitoneally with a combination of 25 micrograms of each of the microencapsulated sub-units. The combined microsphere formulation induced both mucosal and systemic immunity. There was an additive effect in combining sub-units and the protection afforded by the combined microencapsulated antigens was superior to that provided by the administration of any single encapsulated antigen and by the existing whole cell vaccine. The protective efficacy of the combined microencapsulated sub-units was further enhanced by co-administering cholera toxin B sub-unit. Microencapsulation of the sub-units offered advantages which included depot release of the vaccine in vivo and the facilitation of oral, intranasal or inhalational delivery. Therefore, immunization with microencapsulated sub-unit antigens was an effective means of generating humoral and cellular responses which endowed protective immunity.