Given recent focus on large rivers as conduits for excess nutrients to coastal zones, their role in processing and retaining nutrients has been overlooked and understudied. Empirical measurements of nutrient uptake in large rivers are lacking, despite a substantial body of knowledge on nutrient transport and removal in smaller streams. Researchers interested in nutrient transport by rivers (discharge >10000 L/s) are left to extrapolate riverine nutrient demand using a modeling framework or a mass balance approach. To begin to fill this knowledge gap, we present data using a pulse method to measure inorganic nitrogen. (N) transport and removal in the Upper Snake River, Wyoming, USA (seventh order, discharge 12000 L/s). We found that the Upper Snake had surprisingly high biotic demand relative to smaller streams in the same river network for both ammonium (NH4+) and nitrate (NO3-). Placed in the context of a meta-analysis of previously published nutrient uptake studies, these data suggest that large rivers may have similar biotic demand for N as smaller tributaries. We also found that demand for different forms of inorganic N (NH4+ vs. NO3-) scaled differently with stream size. Data from rivers like the Upper Snake and larger are essential for effective water quality management at the scale of river networks. Empirical measurements of solute dynamics in large rivers are needed to understand the role of whole river networks (as opposed to stream reaches) in patterns of nutrient export at regional and continental scales.