Induction of systemic immune responses after intraperitoneal inoculation of poly(L)lactide microspheres containing the V antigen of Yersinia pestis co-encapsulated with IFN-γ were investigated. Serum antibody responses and T cell proliferative responses were measured in groups of Balb/c mice which were injected intraoperitoneally with single or double emulsion preparations of either V/IFN-γ or V alone in a range of dose levels. Groups which received V antigen co-encapsulated with IFN-γ produced higher V-specific antibody responses, predominantly of the IgG1 isotype. Administration of 25 μg V/IFN-γ in a single emulsion resulted in a significantly increased (p < 0.05) splenic T cell proliferative response to V antigen compared with other formulations. It was concluded that IFN-γ co-encapsulated with V antigen in poly(L)lactide microspheres acted as an adjuvant and increased antigen specific systemic immune responses. Therefore, co-encapsulation with IFN-γ may result in effective single dose vaccines by increasing the immunogenicity of the formulations.