Pathways and densities of descending vasa recta (DVR) and ascending vasa recta (AVR) in the outer zone of the inner medulla (IM) were evaluated to better understand medullary countercurrent exchange. Nearly all urea transporter B (UT-B)-positive DVR, those vessels exhibiting a continuous endothelium, descend with little or no branching exclusively through the intercluster region. All DVR have a terminal fenestrated (PV-1-positive) segment that partially overlaps with the UT-B-positive segment. This fenestrated segment descends a distance equal to approximately 15% of the length of the connecting UT-B-positive segment before formation of the first branch. The onset of branching is indicative of vessel entry into the intracluster region. The number density of UT-B-positive DVR at 3,000 mum below the OM-IM boundary is approximately 60% lower than the density at 400 mum below the OM-IM boundary, a result of DVR joining to fenestrated interconnecting vessels and an overall decline in UT-B expression. AVR that lie in the intercluster region (designated AVR(2)) lie distant from CDs and ascend to the OM-IM boundary with little or no branching. AVR(2a) represent a subcategory of AVR(2) that abut DVR. The mean DVR length (combined UT-B- and PV-1-positive segments) nearly equals the mean AVR(2a) length, implying a degree of overall equivalence in fluid and solute countercurrent exchange may exist. The AVR(2)/DVR ratio is approximately 2:1, and the AVR(2a)/DVR ratio is approximately 1:1; however, the AVR/DVR ratio determined for the full complement of fenestrated vessels is approximately 4:1. The excess fenestrated vessels include vessels of the intracluster region (designated AVR(1)). Countercurrent exchange between vasa recta occurs predominantly in the intercluster region. This architecture supports previous functional estimates of capillary fluid uptake in the renal IM.