The immune response in rats to gamma-irradiated human amnion and human skin collagen was characterized through histologic and immunologic methods. Pepsin-extracted human amnion collagen and skin collagen were purified and reconstituted. Implants of amnion collagen demonstrated greater persistence than skin collagen. For amnion collagen implants, no significant inflammatory response was found. Fibroblast and adipocyte ingrowth and neovascularization were present. Conversely, obvious inflammatory infiltration was evident in the skin collagen implants. Enzyme-linked immunosorbent assay results showed that anti-amnion collagen antibody levels were significantly lower than anti-skin collagen antibody levels against their respective implant materials. The ratios of type I to type III collagen are 56:44 and 95:5 for amnion collagen and skin collagen, respectively. These findings suggest that in this heterologous type system, type III collagen-rich amnion collagen preparations appear superior to skin collagen for soft-tissue augmentation.