PURPOSE. To determine the immunogenic characterization of amniotic epithelium (AE), by examining the fate of allogeneic AE grafts heterotopically transplanted in the eye. METHODS. Intact AE from enhanced green fluorescence protein (EGFP) transgenic mice (C57BL/6 background) and wild-type C57BL/6 mice were transplanted onto cornea or conjunctiva, or inserted into the anterior chamber (AC) of normal BALB/c mice, C57BL/6 mice, or BALB/c mice presensitized to donor antigens. For repeated AE transplantation experiments, AE was grafted in the other eye 7 days after the first grafting. Graft fate was assessed clinically and histologically at selected intervals after grafting. Infiltrating inflammatory cells were examined immunohistochemically. Sensitization to alloantigens by AE was assessed by the delayed hypersensitivity (DH) response. RESULTS. In normal recipients, GFP ϩ cells were absent in EGFP donor-derived AE grafts by day 21 on cornea and by day 7 on conjunctiva. AE grafts implanted in the AC survived for Ͼ8 weeks. In presensitized recipients and recipients that underwent repeated AE implantation, graft survival was markedly shorter than in normal recipients. DH was induced at 2 weeks, but failed to be induced at 4 weeks after grafting on cornea or at 8 weeks after grafting on conjunctiva and in the AC of normal recipients. CONCLUSIONS. Fresh allogeneic AE expressed immunogenicity when placed on the ocular surface, although no memory of allospecific DH was acquired. Allogeneic AE is clearly vulnerable to immune rejection in specifically sensitized recipients