Southern blotting and multiple restriction enzymes were used to analyze T-cell receptor (TCR) and immunoglobulin heavy chain genes in 20 postthymic T-cell neoplasms, ten prethymic and thymic T-cell tumors, and 45 cases of precursor-B acute lymphoblastic leukemia (ALL). Immunoglobulin heavy chain, never rearranged in a postthymic specimen and only once in a prethymic/thymic sample, was rearranged in all but two cases of precursor-B ALL. In contrast, biallelic rearrangement of TCR beta with deletion of the first constant region germline fragment was regularly seen in T-cell neoplasms, but only twice in the 45 precursor-B ALL cases. TCR gamma was rearranged in all but one postthymic sample, in all prethymic/thymic samples, and in approximately half of precursor-B ALL specimens as well. Preferential use of V gamma regions was evident among the various disorders: V8 and V10 in postthymic neoplasms; and V3, V5, V7, and, particularly, V9 in precursor-B ALL. In all the studied conditions, TCR delta was rarely in germline configuration. Extensive biallelic deletion of J delta 1, J delta 2, and C delta, almost always (19 of 20 specimens) present in postthymic neoplasms, was observed in only a minority (14 of 45) of precursor-B ALL samples. In precursor-B ALL, rearranged antigen receptor genes were more frequently found in common acute lymphoblastic leukemia antigen-positive and terminal deoxynucleotidyl transferase-positive specimens. Furthermore, TCR gene rearrangement in that disorder was characterized by a hierarchical pattern: TCR beta was not rearranged without TCR gamma nor TCR gamma without TCR delta. Despite uncertainty of the mechanism, the various disorders can be distinguished on the basis of characteristic antigen receptor gene patterns.