The early responses of CD4+ T cells to particle-mediated DNA immunisation were investigated using OVA-specific TCR-transgenic CD4+ T cells. Following adoptive transfer of these cells, mice were immunised by delivery into the skin of a plasmid encoding ovalbumin. Transgenic T cells underwent a rapid and transient antigen-specific activation, followed by clonal expansion (up to approximately 6% of total lymphocytes). Immunisation with ovalbumin in CFA evoked similar responses with slightly faster kinetics. Numerous antigen-specific T cells synthesising IFN-gamma (Th1) and IL-4 (Th2) were detectable using both intracellular staining and ELISPOT assays. This study provides a quantitative analysis of both T cell proliferation and Th1/Th2 balance following particle-mediated DNA immunisation and establishes a robust and sensitive model in which to assess modulation of helper T cell responses in DNA vaccination.