Tumor-associated carbohydrate antigens are considered important targets in efforts to develop cancer vaccines. To further enhance vaccine efforts, we are developing peptide mimotopes of tumor-associated carbohydrate antigens that can elicit functional immune responses. Mapping peptide epitopes with anticarbohydrate antibodies can lend to defining structural relationships that can go undetected by screening of carbohydrate antigens alone. Here we contrast reactivity patterns for peptides using monoclonal antibodies (MAbs) directed to the neolactoseries related Lewis Y (LeY) and sialyl-Lewis X (sLeX) antigen and the GD3/GD2 ganglioside antigen. We observe that representative MAbs cross-react with a WRY-containing peptide and that this motif type is isolated by the respective monoclonal in peptide phage display screening. Primary immunization with multiple antigen peptide preparations with QS-21 adjuvant efficiently elicited cytotoxic IgM antibodies for a murine Meth A fibrosarcoma line expressing sLeX. The cytotoxicity of IgG polyclonal response was found to be as effective as IgM in mediating complement-dependent cytotoxicity against the Meth A line. These experiments suggest that peptide mimotopes of the LeY and sLeX tumor-associated carbohydrate antigen and QS-21 adjuvant could be considered as an immunogenic therapeutic vaccine in carcinoma and melanoma patients in the minimal residual disease setting.