Fourteen human heart valve allografts were examined by light and electron microscopy following their surgical removal 26 to 65 months after insertion. Cusp rupture was the most common reason (78.5%) for replacement of the allografts, which had been sterilized either with beta propiolactone or ethylene oxide before insertion. The deep surface of the grafts showed invasion by lymphocytes, plasma cells, macrophages and capillary loops. A sheath of host tissue extended from the margin of the orthotopic aortic grafts toward, and sometimes just onto, the base of the cusps. Although most of the allograft tissue lacked intact fibroblasts or endothelial cells, it contained widely scattered cell debris. Focal collections of mononuclear cells including macrophages, lay in zones of homogeneous eosinophilic matrix in the cusps of all but one graft, and infiltration by fibrin, erythrocytes and leucocytes was common. These changes were present in all but one of the cusps which had ruptured. It is suggested that local factors may permit infiltration by mononuclear cells and deposition of fibrin, which coincidentally weaken the cusp, predisposing to its rupture. Fourteen human heart valve allografts were examined by light and electron microscopy following their surgical removal 26 to 65 months after insertion. Cusp rupture was the most common reason (78.5%) for replacement of the allografts, which had been sterilized either with beta propiolactone or ethylene oxide before insertion. The deep surface of the grafts showed invasion by lymphocytes, plasma cells, macrophages and capillary loops. A sheath of host tissue extended from the margin of the orthotopic aortic grafts toward, and sometimes just onto, the base of the cusps. Although most of the allograft tissue lacked intact fibroblasts or endothelial cells, it contained widely scattered cell debris. Focal collections of mononuclear cells including macrophages, lay in zones of homogeneous eosinophilic matrix in the cusps of all but one graft, and infiltration by fibrin, erythrocytes and leucocytes was common. These changes were present in all but one of the cusps which had ruptured. It is suggested that local factors may permit infiltration by mononuclear cells and deposition of fibrin, which coincidentally weaken the cusp, predisposing to its rupture.