The structure of immunoglobulin heavy chain (IgH) and T cell antigen receptor (TCR) beta and gamma chain genes was studied in 38 cases of adult and two cases of childhood acute lymphoblastic leukemia (ALL). Seven cases of T-ALL all showed clonally rearranged TCR beta and gamma genes; only one of these also contained rearranged IgH genes. All precursor B cell ALLs and one case of unusual B cell ALL/lymphoma had clonally rearranged IgH genes, but a high proportion (22 of 32, 69%) of precursor B cell ALLs also had rearrangement of TCR beta and/or gamma genes. TCR beta gene rearrangement was less common in more mature precursor B cell ALL, expressing cytoplasmic IgM (pre-B-ALL) (0 of 5) than in other precursor B cell ALL cases (15 of 27). In the precursor B cell ALLs overall, 10 (32%) had rearrangement of both beta and gamma genes, while 7 (22%) had rearrangement of TCR gamma genes only. A further 5 (16%), all expressing one or more unusual immunophenotype markers, had TCR beta gene rearrangement without detectable gamma gene rearrangement. These observations, together with certain characteristics of constant-joining region usage of both TCR genes (a preference for rearrangement into the C beta 2 and C gamma 1 genes), distinguishes these "inappropriate" rearrangements from those found in T-ALL and suggests that they have arisen through a differentiation arrest which is not part of a normal T cell developmental program.