In addition to conventional morphological, histological and immunological marker studies, cells from 150 children with leukemia or non Hodgkin's lymphoma were analysed using the Southern blot hybridization technique to examine immunoglobulin- (Ig) and T-cell receptor (TCR) gene rearrangements. Patients with B-lineage leukemia or NHL demonstrated in 90% an Ig heavy chain gene rearrangement, 6% with an additional light chain kappa gene rearrangement. Combined Ig- with TCR-beta-gene rearrangements were mainly found in patients with common ALL: 19% at first presentation, and 33% in relapse. Moreover, 6 c-ALL patients showed rearrangements in all 3 gene loci (JH-, Ck- and TCR). Based on the developmental hierarchy of Ig- and TCR gene rearrangements it was possible to further subclassify c-ALL into different stages of B cell development. No correlation could be established between the different constellations of gene rearrangements, the number of rearranged fragments and the course of illness. All patients with T-lineage leukemia or NHL demonstrated TCR rearrangements of the beta-, g- and delta-gene loci, two with an additional Ig gene rearrangement. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms. Furthermore, non-germline configuration was found in tumor cells of every patient with AUL, O-ALL and AHL, permitting a classification to B- or T-cell lineage. Noteworthy is that every AML patient with Ig- and/or TCR gene rearrangements showed a poor or non-response towards therapy. Specimens of individual patients with differently involved tissues at diagnosis always showed an identical rearrangement. The intensity depended on the number of infiltrating blast cells.(ABSTRACT TRUNCATED AT 250 WORDS)