To examine the impact of the complex radial organization of the rat outer medulla (OM) on the distribution of nitric oxide (NO), superoxide (O 2-) and total peroxynitrite (ONOO), we developed a mathematical model that simulates the transport of those species in a cross section of the rat OM. To simulate the preferential interactions among tubules and vessels that arise from their relative radial positions in the OM, we adopted the region-based approach developed by Layton and Layton (Am J Physiol Renal Physiol 289: F1346-F1366, 2005). In that approach, the structural organization of the OM is represented by means of four concentric regions centered on a vascular bundle. The model predicts the concentrations of NO, O2-, and ONOO in the tubular and vascular lumen, epithelial and endothelial cells, red blood cells (RBCs), and interstitial fluid. Model results suggest that the large gradients in PO2 from the core of the vascular bundle toward its periphery, which stem from the segregation of O2-supplying descending vasa recta (DVR) within the vascular bundles, in turn generate steep radial NO and O2- concentration gradients, since the synthesis of both solutes is O2 dependent. Without the rate-limiting effects of O2, NO concentration would be lowest in the vascular bundle core, that is, the region with the highest density of RBCs, which act as a sink for NO. Our results also suggest that, under basal conditions, the difference in NO concentrations between DVR that reach into the inner medulla and those that turn within the OM should lead to differences in vasodilation and preferentially increase blood flow to the inner medulla. Copyright © 2010 the American Physiological Society.