B-cell malignancies, such as malignant lymphoma and chronic lymphocytic leukemia, commonly present with advanced disease and multiple sites of involvement. Consequently, systemic combination chemotherapy is the standard therapeutic approach and cures about one half of these patients. Development of novel therapies is required if the remaining patients are to be cured of their malignancy. Lym-1, a mouse monoclonal antibody that is reactive with these malignancies, has been coupled with 131I or 67Cu and used to treat 55 patients with advanced B-cell malignancies that had proven resistant to standard therapy. The majority of the patients responded to this therapy and the survival of responders was longer than that of non-responders. Similar results have recently been reported by others. These results represent a remarkable achievement for single agent therapy because these trials were exploratory in nature and most of the patients had failed many chemotherapy regimens. The toxicities were in general mild and readily manageable. It appears that enhancing strategies are likely to improve upon these results by increasing the therapeutic index.