OBJECTIVE To study the effect of combined application of external cyclosporine A (CsA) and CTLA4Ig in inhibiting rejection and inducing immune tolerance in composite tissue allograft. METHODS: The auricles with vessel pedicle were transplanted from Lewis rats to BN rats under microsurgery. CsA was spreaded on the surface of grafts in combination with administration of CTLA4Ig intraperitoneally after transplantation. The rejection response and survival time of grafts were observed, and the IL-2 level in serum was measured. RESULTS: The mean survival time was (7.8 +/- 1.7) days in control group. It was (15.2 +/- 1.9) days when recipients treated by CsA and (16.6 +/- 2.1) days by CTLA4Ig. Under the combination of CsA and CTLA4Ig, the mean survival time was significantly prolonged to (28.8 +/- 3.5) days (P lt; 0.05) with the lowest level of IL-2 in serum of recipients. CONCLUSION: The combined application of external CsA and CTLA4Ig inhibits rejection of allograft effectively, which can be a favorable therapy on composite tissue allo-transplantation.