The SCL/tal-1 gene on chromosome 1 is disrupted in up to 30% of immature T-cell malignancies, thus representing the most commonly recognized chromosomal abnormality in this disorder. Abnormalities of the gene occur rarely by chromosomal translocation into the T-cell receptor (TCR) delta locus and commonly by a site-specific 95-kb deletion, SIL-SCL (tald). Analysis of the SIL-SCL deletion by Southern blotting and polymerase chain reaction (PCR) in a series of 52 immature T-cell malignancies showed a type A deletion in 21% of cases, but no type B deletions. The type A deletion correlated with malignancies of the TCR alpha beta lineage, either on the basis of TCR alpha beta expression or bilateral TCR delta deletion. Fifty percent (5 of 10) of TCR alpha beta-expressing cells demonstrated the abnormality, whereas 0% (0 of 11) of TCR gamma delta-expressing cells did so. Six of eight SIL-SCL type A cases had undergone bilateral delta deletion, whereas only one of 31 cases with an apparently normal SCL gene had done so. These data demonstrate an association between SCL disruption and TCR alpha beta lineage differentiation and suggest that the SIL-SCL deletion occurs at the same stage of ontogeny as TCR delta deletion.