In order to improve the level of sensitivity and specificity of detection of bone marrow minimal residual disease in the acute lymphoid leukemias, we have performed amplification by the polymerase chain reaction of T cell receptor gamma chain gene rearrangements. Cloning and sequencing of amplified leukemic DNA allowed the construction of a clone-specific anti-junctional oligonucleotide to be used for subsequent detection of minimal infiltration by this clone. Using such an oligonucleotide, it was possible to distinguish clonal DNA from polyclonal T lymphocytes and to detect infiltration by this clone at 10(-6) dilution into germline DNA. We therefore describe a generally applicable method for the detection of minimal residual disease in both T-ALL and the majority of B lineage ALLs.