To increase the efficiency of producing monoclonal antibodies to tumor-associated antigens, we have used immunogens which are: 1) depleted of highly immunogenic non-tumor-associated components, 2) enriched in tumor-associated components, and 3) presented in an immunogenic fashion. Selective peripheral protein extracts from colon adenocarcinoma have been combined with insolubilized lectins. These immunogens, when compared to whole cells or crude membranes, elicited far more hybridomas with specificity to tumor-associated antigens. Unexpectedly, we also found a subclass restriction based upon the lectin used for immunoperoxidase techniques and have found minimal or no normal tissue reactivity but with extensive reactivity to adenocarcinomas of the colon, lung, and breast. These methods have considerable potential for producing monoclonal antibodies which may be useful in therapy and diagnosis.