Specific structural rearrangements involving chromosome band 11q23 occur in a variety of hematologic malignancies, including an estimated 2-7% of patients with acute lymphoblastic leukemia (ALL). Translocations involving chromosome band 11q23 have been associated with a poor prognosis in patients with ALL. Recently, a gene known as MLL has been identified which is involved in acute lymphoid and myeloid leukemias with rearrangements at 11q23. A 0.74-kilobase (kb) cDNA probe from the MLL gene can detect both common and uncommon rearrangements involving MLL on conventional Southern blots. We studied 86 newly diagnosed adults entered on an ALL clinical trial to investigate the incidence of MLL gene rearrangements and to determine clinical, morphologic, immunologic and cytogenetic characteristics of such patients. Two of 86 patients had MLL gene rearrangements detected by Southern blot analysis. One of these 86 patients had an 11q23 translocation by cytogenetic analysis whereas the second patient was unevaluable by standard cytogenetic analysis. Southern blot identification of rearrangements involving MLL, especially in patients with limited material for cytogenetic analysis, can provide critical diagnostic and prognostic information which may be useful in the clinical management of patients with these abnormalities.