The Neuse River and Estuary, a major tributary of the second largest estuary on the United States mainland, historically has sustained excessive blooms of algae and toxic dinoflagellates, hypoxia, and fish kills. Previous attempts have been made to use shortterm databases of 2-3 years, or data sets from infrequent (monthly) sampling, to assess whether nutrient inputs to the Neuse are increasing and supporting higher algal production. These previous efforts also have relied on single-point-determined flow velocity data, at upstream sites remote from the estuary, to estimate the volume of flow in quantifying nutrient loading to the estuary. We completed a five-year study of the Neuse, including a comparative inventory of nutrients to the watershed from point sources and from concentrated animal operations (CAOs) as recent nonpoint sources, as well as an intensive assessment of water quality over time in the mesohaline estuary. Estimates of nutrient loads were based on volume of flow data from shore-to-shore transect cross sections, taken with a boat-mounted acoustic Doppler current profiler at the westernmost edge of the estuary.A total of 441 point dischargers contributed at least 3.34 ϫ 10 8 L effluent/d to the Neuse system, much of which came from municipal wastewater treatment plants (2.03 ϫ 10 8 L effluent/d, excluding periods of plant malfunctions; total annual loadings of at least 9 ϫ 10 5 kg P and 2.1 ϫ 10 6 kg N, with a 17% increase in human population over the past decade). The Neuse basin also included 554 CAOs, with 76% in swine production (1.7 ϫ 10 6 animals, from a 285% increase in the past decade) and 23% in poultry (5.5 ϫ 10 5 animals). An estimated 5.9 ϫ 10 9 kg manure produced by swine and poultry during 1998 contributed ϳ4.1 ϫ 10 7 kg N and 1.4 ϫ 10 7 kg P to the Neuse watershed. About 20% of the area in the watershed now has enough manure from CAOs to exceed the P requirements of all nonlegume crops and forages. About two-thirds of the N-and P-rich feeds for these animals are imported (with 4.0 ϫ 10 7 kg N and 1.6 ϫ 10 7 kg P in 1998); thus, the watershed increasingly has become a nutrient sink. Over the five-year study in the Neuse Estuary study area, P loading significantly declined (by an estimated 14%), whereas TN (total nitrogen) loading significantly increased (by an average of 16%) and TN i (total inorganic nitrogen) increased by ϳ38%. The increased inorganic N (N i ), partly related to severe storms with high precipitation in years 4-5, coincided with a decrease in phytoplankton biomass (as chlorophyll a) that likely reflected displacement/washout of algal populations and cysts. Thus, while both N and P supplies have increased in the watershed, there is evidence for a significant increase in N i loading but, as yet, no apparent signal for increased P in the lower estuary.Weather patterns ultimately control when/whether the elevated N i supply will support increased algal production, so that estuarine algal blooms, hypoxia, and fish kills will remain difficult, at best, to predict in mode...