Many antigens recognized by autologous T lymphocytes have been identified on human melanoma. Melanoma patients usually mount a spontaneous T cell response against their tumor. But at some point, the responder T cells become ineffective, probably because of a local immunosuppressive process occurring at the tumor sites. Therapeutic vaccination of metastatic melanoma patients with these antigens is followed by tumor regressions only in a small minority of the patients. The T cell responses to the vaccines show correlation with the tumor regressions. The local immunosuppression may be the cause of the lack of vaccination effectiveness that is observed in most patients. In patients who do respond to the vaccine, the antivaccine T cells probably succeed in reversing focally this immunosuppression and trigger a broad activation of other antitumor T cells, which proceed to destroy the tumor.