Dipeptidyl peptidase IV (DP IV, CD26) plays an essential role in the activation and proliferation of lymphocytes, which is shown by the immunosuppressive effects of syn-thetic DP IV inhibitors. Similarly, both human immuno-deficiency virus-1 (HIV-1) Tat protein and the N-terminal peptide Tat(1–9) inhibit DP IV activity and T cell prolifer-ation. Therefore, the N-terminal amino acid sequence of HIV-1 Tat is important for the inhibition of DP IV.