In this study, the potential of the bare skin as a non‐invasive route for vaccination was examined. Following application of heat‐labile enterotoxin (LT) of Escherichia coli onto bare skin of BALB/c mice, strong serum anti‐LT antibody responses were observed, and mucosal immunoglobulin A (IgA) and IgG antibodies were measured in vagina washes. In addition, LT enhanced the serum and mucosal antibody and proliferative T‐cell responses to the model protein antigen β‐galactosidase (β‐gal) when coadministered onto bare skin, highlighting its potential to exert an adjuvant effect. When a peptide representing a T‐helper epitope (aa 307–319) from the haemagglutinin of influenza virus was applied onto bare skin with LT or cholera toxin (CT), it primed effectively peptide‐ and virus‐specific T cells, as measured in vitro by the interleukin‐2 (IL‐2) secretion assay. LT was shown to be as immunogenic as CT. Binding activity to GM1 gangliosides was essential for effective induction of anti‐CT serum and mucosal antibody responses. Finally, mice immunized onto bare skin with LT were protected against intraperitoneal challenge with a lethal dose of the homologous toxin. These findings give further support to a growing body of evidence on the potential of skin as a non‐invasive route for vaccine delivery. This immunization strategy might be advantageous for vaccination programmes in Third World countries, because administration by this route is simple, painless and economical.