An increase in the flux of nitrogen from the Mississippi river during the latter half of the twentieth century has caused eutrophication and chronic seasonal hypoxia in the shallow waters of the Louisiana shelf in the northern Gulf of Mexico. This has led to reductions in species diversity, mortality of benthic communities and stress in fishery resources. There is evidence for a predominantly anthropogenic origin of the increased nitrogen flux, but the location of the most significant sources in the Mississippi basin responsible for the delivery of nitrogen to the Gulf of Mexico have not been clearly identified, because the parameters influencing nitrogen-loss rates in rivers are not well known. Here we present an analysis of data from 374 US monitoring stations, including 123 along the six largest tributaries to the Mississippi, that shows a rapid decline in the average first-order rate of nitrogen loss with channel size-from 0.45 day-1 in small streams to 0.005 day-1 in the Mississippi river. Using stream depth as an explanatory variable, our estimates of nitrogen-loss rates agreed with values from earlier studies. We conclude that the proximity of sources to large streams and rivers is an important determinant of nitrogen delivery to the estuary in the Mississippi basin, and possibly also in other large river basins.