We explored the biocompatibility of fluidized canine small-intestinal submucosa (SIS) for periureteral injection and as a patch graft for bladder augmentation in pigs. Gross evaluation 8 weeks after submucosal injection showed persistence of the nodule. Histologic examination showed thickened submucosa with spindle cells embedded in poorly organized fibrous material. There was no evidence of inflammatory reaction or granuloma formation. Subserosal nodules likewise persisted and demonstrated capillary ingrowth. Grafts of SIS became epithelialized within 3 weeks with maintenance of bladder capacity. Ingrowth of capillaries and smooth muscle could be seen in later specimens. Although further studies with longer follow-up are needed, SIS appears to be a promising graft material in the urinary tract.