Acute lymphoblastic leukemias (ALLs) represent the clonal expansion of a lymphoid precursor cell. Therefore, all cells of an ALL should have identical antigen receptor gene rearrangements. In a patient with diploid ALL of the B-cell precursor immunophenotype, seven different clonal rearrangements of the immunoglobulin heavy-chain genes (IgH) were identified, implying the presence of oligoclonal populations. All of these rearrangements were only detectable after a modification of the polymerase chain reaction for the complementarity determining region of the IgH genes using V(H) gene framework 3 and (H) consensus primers. Sequence analysis showed that these rearrangements were completely unrelated to each other. Only two of these rearrangements were detectable by Southern blot analysis. Quantification and single-cell analysis confirmed the high frequency of these latter two rearrangements, as well as their presence in the same clonal population. The other rearrangements characterized less than 5% of the leukemic population. In addition, two T-cell receptor Vdelta2-Ddelta3 (TCRdelta) rearrangements were identified, both at a similar frequency. However, they were derived from different cells. An Igkappa rearrangement represented the only clonal marker in this leukemia. All of the Ig and TCRdelta rearrangements, with the exception of one IgH rearrangement, remained stable throughout the course of the disease. The persistence of such a great number of distinct IgH rearrangements at different quantities within the leukemic population and of the two biclonal TCRdelta rearrangements is compatible with the presence of a clonal disease that is defined by the Igkappa rearrangement.