Multiple myeloma is a malignancy of plasma cells that accounts for 1% of cancers worldwide and is treatable, yet incurable. U266 is an IgE-secreting, IL-6-producing human multiple myeloma cell line, against whose unique surface markers we have tried to raise monoclonal antibodies (MAbs). Female Balb/c mice (6 weeks old) were immunized through two routes of administration, with three different antigenic concentrations. Fusion efficiencies and specific efficiencies for the three antigenic concentrations were calculated. It was found that while an initial immunogen concentration of 10 microg gave the best fusion efficiency of 63.89%, an initial immunogen concentration of 15 microg resulted in the best specific efficiency of 54.54%. Out of the 147 supernatants selected for screening, 66 were found reactive to common surface proteins of non-malignant human plasma cells and seven were myeloma-specific MAbs. These MAbs have a range of potential applications in multiple myeloma imaging, phenotyping, and possible targeted therapy.