The study investigates the role of a cell surface molecule, APO-1, in controlling the growth of malignant lymphocytes. Monoclonal antibodies (MAbs) against APO-1 were developed and found to react with a 52-kilodalton antigen on activated human lymphocytes, malignant lymphocyte lines, and some patient-derived leukemic cells. These MAbs blocked cell proliferation and induced apoptosis, characterized by changes in cell morphology and DNA fragmentation. The induced apoptosis was distinct from complement-dependent cell lysis and was mediated solely by the antibody. In vivo, a single intravenous injection of anti-APO-1 into nu/nu mice carrying a human B cell tumor induced rapid regression of the tumor, with histological evidence of apoptosis. The findings suggest that induction of apoptosis through APO-1 may be a therapeutic approach for treating malignancy.The study investigates the role of a cell surface molecule, APO-1, in controlling the growth of malignant lymphocytes. Monoclonal antibodies (MAbs) against APO-1 were developed and found to react with a 52-kilodalton antigen on activated human lymphocytes, malignant lymphocyte lines, and some patient-derived leukemic cells. These MAbs blocked cell proliferation and induced apoptosis, characterized by changes in cell morphology and DNA fragmentation. The induced apoptosis was distinct from complement-dependent cell lysis and was mediated solely by the antibody. In vivo, a single intravenous injection of anti-APO-1 into nu/nu mice carrying a human B cell tumor induced rapid regression of the tumor, with histological evidence of apoptosis. The findings suggest that induction of apoptosis through APO-1 may be a therapeutic approach for treating malignancy.