Percutaneous peptide immunization is a method in which tumor-specific cytotoxic T lymphocytes (CTL) are primed in the lymph nodes and spleen following application of tumor peptides to corneum barrier-disrupted murine skin. Immunized mice are protected against subsequent challenge with corresponding tumors and suppress the growth of established tumors. CTL expansion after peptide application seems to be mediated by epidermal Langerhans' cells. In the human, disruption of permeability barrier by tape stripping also induces activation of epidermal Langerhans' cells. Thus, percutaneous peptide immunization provides a simple and noninvasive means of inducing potent antitumor immunity that may be exploited for cancer immunotherapy in the human.