Effects on hyperacute rejection were studied in a discordant model with the platelet GPIIb/IIIa antagonist Reopro. Pig kidneys perfused with human blood survived median 118 min in the Reopro group and 103 min in the controls (P = 0.22). Platelet and leukocyte counts decreased, whereas plasma thrombospondin and soluble as well as platelet membrane P-selectin increased significantly in both groups without significant intergroup differences. beta-Thromboglobulin and myeloperoxidase increased significantly more in the control group than in the Reopro group (P = 0.009 and P = 0.02, respectively). The classical complement pathway was substantially and similarly activated in both groups. Light and electron microscopy revealed arterial thrombi and numerous glomerular platelet aggregates in the control group in contrast to the Reopro group. In conclusion, Reopro reduced platelet aggregation, and platelet and leukocyte activation to some extent, but had no effect on complement activation and did not significantly prolong xenograft survival, even though better preservation of morphology was shown.