INTRODUCTION AND OBJECTIVES: The extrinsic efferent and afferent neural pathways to and from the human urinary bladder are well defined but the location and arborization of these nerves as they traverse the serosa, muscularis and urothelial layers are not. Such information could have significant clinical implications for interventions directly targeting these nerves or attempting to preserve them. The purpose of this study was to create a three dimensional map of the innervation of the human urinary bladder from the extrinsic perivesical adventitial nerve trunks to the urothelium. METHODS: 3 human bladders (2 female, 1 male) were harvested from fresh frozen cadavers and fixed in formalin. Five micron sections were created with every 20th slide used for staining with S100 antibody and incorporation into the model. Slides were scanned and arranged using Adobe Photoshop and then the 3 dimensional map was created using Amira software. RESULTS: A detailed map of neural pathways into the bladder has been generated. An area of high nerve density is seen around each ureteral orifice and ureteric ridge as expected (Fig. 1). The lower branches appear to penetrate at approximately 3 and 9 o’clock of the bladder neck and extend upward along the lateral edges of the trigone. The nerves run throughout the bladder adventitia and anterior vaginal wall (colored teal) with penetration into the detrusor (blue) at the ureteric ridge and bladder neck (Fig. 2). Innervation is most dense at the bladder neck at the 3 and 9 o’clock positions, and at the level of the interureteric ridge with the nerves running primarily within the adventitial layer. The nerves primarily penetrate the detrusor at the bladder neck and interureteric ridge region of the bladder. CONCLUSIONS: A 3 dimensional map of human bladder innervation may provide guidance to more precisely direct neuromodulatory or neuroablative interventions for many vesical disorders. In addition, it may impact on surgical reconstruction or subtotal bladder resection procedures where nerve preservation is critical. Source of Funding: This work was supported by a grant from Allergan, Inc.