In immunologically defined National Institutes of Health miniswine, a segment of internal jugular vein was anastomosed to the carotid artery as an interposition graft. Patency of swine major histocompatibility complex matched, one haplotype mismatched, and complete mismatched veins was 9.8, 6.3, and 3.0 weeks respectively (p = 0.009). More than 90% of mismatched and 20% of matched allografts developed a positive crossmatch before occlusion (p = 0.006). The mixed lymphocyte response did not predict graft occlusion. Treatment of 10 swine with cyclosporine (10 mg/kg/day) did not significantly improve patency for one haplotype mismatched grafts. In haplotype mismatched veins, cryopreserved grafts occluded more rapidly than noncryopreserved grafts: mean 2.4 versus 6.3 weeks, respectively (p = 0.002). In all cryopreserved vein grafts, alloantibody appeared at or after graft occlusion rather than before occlusion as seen with fresh allografts (p = 0.046). The mean patency of cryopreserved versus fresh autografts was 3.3 and greater than 32 weeks, respectively (p = 0.004). In summary, these results indicate that (1) allograft patency is related to the degree of swine major histocompatibility complex match and development of cytotoxic alloantibodies; (2) moderate-dose cyclosporine does not prolong allograft patency nor suppress development of antibody; (3) cryopreservation may accelerate graft occlusion through nonimmunologic mechanisms.