ICC were first discovered by Ramon y Cajal in the intestine in 1911 using methylene blue and Golgi staining techniques (Cajal, 1911) and are now established as pacemakers and mediators of neurotransmission (Sanders, 1996). It was previously believed that ICC were present in only the gastrointestinal tract but there is now convincing evidence that the urinary tract, including the urethra, urinary bladder, renal pelvis and ureters also contain populations of cells with many characteristics of ICC, though these studies are at a comparatively early stage (Brading and McCloskey, 2005). The aim of the present study was to: identify interstitial cells of Cajal (ICC) in the wall of the guinea-pig bladder using transmission electron microscopy and antibodies to the Kit receptor conjugated to nanogold particles; to characterize the ultrastructural properties of bladder ICC and to examine their relationships with nerves and smooth muscle cells. Bladders were removed from guinea-pigs (n=4), killed by cervical dislocation in accordance with Schedule 1, UK Home Office regulations. Bladder tissues were prepared for transmission electron microscopy using standard protocols. Kit-positive ICC were identified in sections from the lamina propria and detrusor, consistent with previous findings with confocal microscopy (Davidson and McCloskey, 2005). In the lamina propria, ICC formed an interconnecting network of branched cells and were also found in close proximity to small blood vessels where their branches made contacts with the vessel wall. In the detrusor, ICC were found on the edge of smooth muscle bundles and the contacts between SMC and ICC were typically 50-100nm. ICC were frequently associated with intramural nerves, again typically within 100nm. Ultrastructurally, ICC contained mitochondria, rough and smooth endoplasmic reticulum, thin and intermediate filaments, caveolae, Golgi apparatus, free ribosomes and cytoplasmic vesicles. They were distinct from fibroblasts by the presence of a basal lamina and differed from smooth muscle cells in the absence of thick filaments and dense bodies. The ultrastructural characteristics of ICC in the guinea-pig bladder were characterized with transmission electron microscopy and were consistent with those of gut ICC. ICC were positively identified with c-Kit antibody labeling in the lamina propria and detrusor regions and were closely associated with each other, nerves and smooth muscle cells, consistent with previous published work (Davidson and McCloskey, 2005) at the light microscope level.