In graftectomy samples from B226 (A, B:day 16, HE stain), thrombi (arrows in A) were seen in capillaries. Polymorphonuclear leukocytes (arrow in B) and mononuclear cells (arrowhead in B) infiltrated the grafts. In graftectomy samples from B214 (C, D: day 59, HE stain), interstitial hemorrhage and multiple microthrombi in the microvasculature developed. In addition to the infiltration of polymorphonuclear leukocytes (arrow in D), focal mononuclear cells (arrowhead in D) infiltrated the graft. In graftectomy samples from B229 (E, H, K: day 78), B223 (F, I, L, N–P: day 110) and B228 (G, J, M: day 179) (E–J: HE stain; inset in G, K–M: EMG stain), multiple microthrombi, an irregular distribution of interstitial hemorrhage and chronic xenograft vasculopathy (arrowheads in E–G) developed along with a focal mononuclear cell infiltrate (H–J). AHXR was characterized by thrombotic microangiopathy with multiple microthrombi in capillaries (arrows in K–M) and arteries (double arrow in K) in the grafts, and by immunoglobulin and complement deposition (N: IgM; 0: C5b-9). Two-color immunostaining for CD41 (red color) and C4d (green color) showed that almost all of the CD41+ thrombi (arrows in P) were detected within vessels that contained deposits of complement. Electron microscopy (Q, R) revealed damaged capillaries in the graft of B228 on day 179 (× 1900). The damage was characterized by the loss of endothelial cells with fibrin thrombi (asterisks in Q) and capillary destruction (arrowheads in R) with interstitial hemorrhage.