The tal-1 proto-oncogene encodes a helix-loop-helix DNAbinding protein that has been implicated in the formation of T cell acute lymphoblastic leukemia (TALL). Patients with TALL harbor structural rearrangements of tal-1 that result from either local DNA deletion or t(1 ;14)(p34;gll) chromosome translocation. By analyzing t(1;14)(p34;gll) chromosomes from a series ofpatients, we have now identified a discrete region of tal-1 wherein most of the translocation breakpoints occur. Moreover, mapping of tal-1 genomic DNA revealed that coding exons are situated on both sides of the t(1 ;14)(p34;gll) major breakpoint region. Hence, the translocated allele of tal-1 is truncated in a manner that reduces its amino acid coding potential. © 1990, Rockefeller University Press., All rights reserved.