CD3+ cells, isolated from peripheral blood of two patients with T cell acute lymphoblastic leukemia (T-ALL), did not react with the monoclonal antibody WT31, which is thought to recognize a framework determinant on the conventional T cell receptor (TcR), consisting of disulfide-linked alpha and beta chains. The T-ALL cells of neither patient synthesized TcR alpha mRNA; the cells of patient DD contained only truncated (D-J) TcR beta mRNA, while the cells of patient HZ contained truncated as well as mature (V-D-J) TcR beta mRNA. The leukemic cells of both patients made TcR gamma mRNA. At the cell surface, the T-ALL cells of patient DD expressed a CD3-associated disulfide-linked dimer, which contained the TcR gamma protein. On the leukemic cells of patient HZ the TcR gamma protein was present as a 41-44-kDa CD3-associated subunit in a noncovalently linked form. The TcR gamma genes in the T-ALL cells of patient DD were rearranged exclusively to the C gamma 1 locus, while in the T-ALL cells of patient HZ both C gamma 1 alleles were deleted and rearrangement to the C gamma 2 locus had occurred. The C gamma 1 gene segment, just like the TcR alpha and TcR beta gene segments, contains a cysteine codon in its second exon. This cysteine residue is involved in the formation of the interchain disulfide bond. The human C gamma 2 gene segment, however, does not contain a cysteine codon in its second exon. The absence of the cysteine residue in C gamma 2 encoded TcR gamma chains explains the lack of an interchain disulfide bond in the TcR on the T-ALL cells of patient HZ. The TcR gene configuration, as well as the expression of model for T cell differentiation in which the TcR gamma gene rearranges first to the C gamma 1 locus prior to or coinciding with D-J joining of the TcR beta gene, followed by rearrangement to the C gamma 2 locus and V-D-J joining of the TcR beta gene.