In support of the idea that the HLA system plays a major role in corneal graft rejection, we report these two unique cases. Both had two penetrating grafts in the same eye. One was a regular graft and the second a patch graft to repair a perforation in the initial one. In the first case, the original graft had an allograft reaction and the patch graft remained unaffected. In the second case, an allograft reaction to the patch graft developed while the regular graft remained completely clear. Both grafts in the two cases cleared following medical therapy. The fact that in these two cases rejection reactions involved one transplant only, even though the other graft was subject to the same conditions, implies that the difference in the antigenicity of the two grafts is an important factor in the chain of events leading to rejection.