The AB4 monoclonal antibody, which recognizes an HLA-DR epitope, was found to bind to a high percentage of malignant blast cells in samples obtained from 27 patients with ALL. These included 11 of 11 cases with c-ALL, 3 of 7 with pre-pre-B, and 8 of 9 cases with pre-B ALL. AB4 was used together with anti CD10 and anti CD19 antibodies and super-paramagnetic particles for developing a direct immunomagnetic procedure for purging human bone marrow of leukemic cells. In model experiments with KM3 cells admixed to mononuclear bone marrow cells, the individual antibodies each removed 2.8-3.1 logs and 3.6-4.1 logs of tumor cells with one and two purging cycles, respectively. In comparison, the efficacy of a mixture of the three antibodies was 4.4 logs with one treatment cycle, and > 5 logs with repeated treatments. Whereas the use of a commercially available anti-HLA-DR antibody resulted in a 90% reduction in the survival of CFU-GMs and normal blast colonies, AB4 had only a moderate effect on the progenitor cells (46% and 30% reduction). In conjunction with autologous transplantation, bone marrow from a patient was purged with the antibody mixture and 50% of the CFU-GMs and 47% of the CD34+ cells remained after treatment. The patient showed a normal engraftment, reaching a level of 0.5 x 109/l neutrophils by day 20 and 20 x 109/l platelets by day 30. It is concluded that the antibody cocktail may safely and effectively be used for rapid autograft purging in patients with c-ALL, and also in phenotypically selected cases with other subtypes of ALL.