With isolated exceptions, the clinical use of venous allografts has been disappointing. Considerable evidence indicates that allograft antigenicity plays a major role in the failure of venous allografts when used as arterial replacements. Recent reports suggest that DMSO-cryopreservation of venous allografts may reduce allograft antigenicity while preserving allograft viability. The present study examines the effect of modifications of vein allografts on subsequent allograft antigenicity. Skin grafts were transplanted from ACI to Lewis inbred strains of male rats. Primary skin graft rejection occurred in 9.0 +/- 1.0 days. Subcutaneous implantation of fresh inferior vena cava from ACI rate into Lewis rats resulted in subsequent skin graft rejection in 5.0 +/- 1.0 days, confirming the antigenicity of venous tissue. Cryopreservation of ACI inferior vena cava for seven days prior to implantation, with or without 15% DMSO, resulted in subsequent skin graft rejection in 5.0 +/- 1.0 days. Treatment of ACI inferior vena cava with 0.30% gluteraldehyde for 20 minutes prior to implantation in Lewis rats resulted in skin graft rejection in 9.0 +/- 1.0 days, the same time as a first set rejection. This study indicates that unmodified veins are normally antigenic and that this antigenicity is not eliminated by cryopreservation with or without DMSO. Gluteraldehyde treatment appears to reduce allograft antigenicity, but results in a nonviable graft. At the present time, there is no known way to reduce the antigenicity of viable venous allografts.