Although the three-dimensional structure of the T-cell receptor (TCR) has not yet been determined, several groups have proposed that the outline structure of the TCR will closely resemble that of immunoglobulin (Ig). Hypervariable regions can be identified within the TCR variable (V) domains, and by analogy to similar regions in the Ig molecule which together form the antigen combining site these have been termed the complementarity determining regions (CDR) 1, 2, and 3. By far the greatest extent of variability occurs at CDR3 and this has led to the proposal that CDR3 is involved in interaction with the peptide bound within the cleft of a major histocompatibility complex (MHC) molecule. We have cloned and sequenced the CDR3 region of several hundred human TCRA and TCRB transcripts from different T-cell populations and studied the amino acid usage in this region. Results show that the average length of the CDR3 region is 10 amino acids with less variation in length than is seen for the Ig heavy chain. There is no difference in CDR3 length between fetal and adult T cells or between CD4 and CD8 populations. The pattern of amino acid usage in the CDR3 region is dissimilar between TCRA and TCRB transcripts. In particular there is a predominance of charged and polar residues in the region of the TCRA transcript thought to interact with peptide. These data provide information on the general pattern of CDR3 length and composition for both TCRA and TCRB.