We have taken advantage of the selection power of phage display technology to define specific peptide mimotopes that recognize individual M- proteins, isolated from patients with multiple myeloma. Preferred amino acid motifs of phages binding to M-proteins were identified in 6/9 patients investigated. Chemically synthesized peptides, corresponding to the phage- displayed peptide inserts, were used to verify the specificity of binding in competition assays. The peptides were able to bind to the M-proteins, as well as the myeloma cells, with high sensitivity and specificity. Employing simple immunological techniques, < 0.01 g/l of M-protein could be quantified, suggesting a novel way for monitoring minimal residual disease in the production of guidelines for adjusting or reintroducing conventional chemotherapy. The peptide mimotopes defined by this technology may be useful as tumour-specific targeting agents and as a tool for purging cells in autologous bone marrow transplantation.