Recently there has been a renewed interest in developing vaccines for use in cancer treatment. Part of this interest stems from a better understanding of the immune system, the identification of a number of T-cell-specific tumor antigens, more effective adjuvants, and the ability to construct more immunogenic molecules using recombinant DNA techniques. Studies from several laboratories have shown that breast cancer patients have preexisting immunity to the HER-2/neu oncoprotein receptor (HER-2) in the form of elevated antibody titers and T-cell immunity. Preclinical studies showed enhanced delayed-type hypersensitivity and cytotoxic T-lymphocyte precursors in spleens from animals immunized with several human leukocyte antigen class I and class II peptides derived from the HER-2 protein. Phase I trials of these peptides combined with the cytokine granulocyte-macrophage colony-stimulating factor as a part of therapy in patients with HER-2-positive cancers have shown minimal local toxicity, along with enhanced helper T-cell activity and antibody production in patients with minimal disease. Increases in cytotoxic T-lymphocyte precursor activity were less frequent, but in some cases could be enhanced when patient lymphocytes were incubated ex vivo with the proinflammatory cytokine interleukin-12. Other preclinical studies designed to enhance HER-2 peptide immunogenicity are in progress. Additional current and future clinical trials using HER-2-derived vaccines will be discussed.