The direct pathway of allorecognition is involved in acute allograft rejection and is characterised by TCR-mediated recognition of the MHC framework; this is thought to occur in a peptide-dependent but not peptide-specific manner. In contrast, the indirect pathway is restricted to the recipient's own MHC molecules and prevails in chronic rejection. In this pathway, the peptide has a major influence on the TCR recognition and selects alloreactive T cells with altered TCR Vbeta usage. However, qualitative analysis of Vbeta usage alone might limit our understanding of alloreactivity. The advantages of a combined quantitative assessment of Vbeta mRNA usage are discussed.