We evaluated here the effect of immunization with a gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) inserted with a helper T cell (Th) epitope, listeriolysin O (LLO) 215-226 derived from Listeria monocytogenes on induction of a specific Th by gene gun bombardment. Immunization of C3H/He mice with pGM215m plasmid encoding murine GM-CSF inserted with LLO 215-226 Th epitope gave the epitope-specific proliferative responses of CD4(+) T lymphocytes. In addition, specific interferon-gamma production from the splenocytes was observed. Concomitantly, pGM215m-immunized mice showed significant protective immunity against lethal listerial challenge. These results suggest that immunization of a gene for GM-CSF inserted with a Th epitope is useful for eliciting a specific Th subset in vivo.