BACKGROUND It has recently been shown that t (12;21) (p13;q 22) is the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL). We have analyzed this translocation in an attempt to evaluate its incidence and to monitor minimal residual disease (MRD) with t (12; 21) rearrangement by detection of TEL-AML1 transcript in patients with childhood ALL. METHODS All cryopreserved bone marrow samples were analyzed using a nested reverse transcription-polymerase chain reaction (RT-PCR) method. TEL-AML1 transcripts were searched for in 34 ALL patients, including six in relapse consecutively diagnosed at our institution between 1991 and 1997. RESULTS TEL-AML1 transcripts were found in five (19%) of 27 patients with B precursor ALL. The patients with BCR-ABL, chromosome 11q23 rearrangement and T-ALL patients did not express TEL-AML1 transcripts. Moreover, MRD in five patients with TEL-AML1 transcripts were analyzed in serial samples. Although TEL-AML1 transcripts disappeared soon after the beginning of chemotherapy in three of the five patients, one patient continued to express them for up to 21 months without recurrence and remained in continuous complete remission for seven years after the cessation of chemotherapy. The remaining patient was admitted to our hospital after the second relapse but died following a failure to induce complete remission. CONCLUSIONS For most patients, the presence of TEL-AML1 transcripts suggests excellent chemosensitivity and a favorable prognosis, but some patients with these transcripts have a different outcome. The present study suggests the possibility that a persistence of MRD is not necessarily related to a relapse of ALL with TEL-AML1 fusion. The prognostic significance of TEL-AML1 transcript remains controversial. Further studies are needed to evaluate the relation between the TEL-AML1 transcript and prognosis.