Nutrients and freshwater delivered by the Mississippi and Atchafalaya Rivers drive algal production in the northern Gulf of Mexico, which eventually results in the widespread occurrence of hypoxic bottom waters along the Louisiana and Texas coast. Researchers have demonstrated a relation between the extent of the hypoxic zone and the magnitude of streamflow, nutrient fluxes, and nutrient concentrations in the Mississippi River, with springtime streamflows and fluxes being the most predictive. In 1999 the U.S. Geological Survey (USGS) estimated the flux of nitrogen, phosphorus, and silica at selected sites in the Mississippi Basin and to the Gulf of Mexico for 1980-1996. These flux estimates provided the baseline information used by the Mississippi River/Gulf of Mexico Watershed Nutrient Task Force to develop an Action Plan for reducing hypoxia in the northern Gulf of Mexico. The primary goal of the Action Plan was to achieve a reduction in the size (areal extent) of the hypoxic zone from an average of approximately 14,000 square kilometers in 1996-2000 to a 5-year moving average of less than 5,000 square kilometers by 2015. Improved statistical models and adjusted maximum likelihood estimation using USGS Load Estimator (LOADEST) software were used to estimate annual and seasonal nutrient fluxes for 1980-2007 at selected sites on the Mississippi River and its tributaries. These data provide a means to evaluate the influence of natural and anthropogenic effects on delivery of water and nutrients to the Gulf of Mexico; to define subbasins that are the most important contributors of nutrients to the gulf; and to investigate the relations among streamflow, nutrient fluxes, and the size and duration of the Gulf of Mexico hypoxic zone. A comparative analysis between the baseline period of 1980-1996 and 5-year moving averages thereafter indicate that the average annual streamflow and fluxes of total nitrogen, nitrate, orthophosphate, and silica to the Gulf of Mexico have decreased. However, the flux of total phosphorus between the baseline period and subsequent 5-year periods has increased. The average spring (April, May, and June) streamflow and fluxes of silica, total nitrogen, nitrate, and orthophosphate to the Gulf of Mexico also decreased, whereas the spring flux of total phosphorus has increased. Similar changes in streamflow and nutrient flux were observed at many sites Buxtonwithin the basin. The inputs of water, total nitrogen, and total phosphorus from the major subbasins of the Mississippi-Atchafalaya River Basin as a percentage of the to-the-gulf totals have increased from the Ohio River Basin, decreased from the Missouri River Basin, and remained relatively unchanged from the Upper Mississippi, Red, and Arkansas River Basins. Changes in streamflow and nutrient fluxes are related, but short-term variations in sources of streamflow and nutrients complicate the interpretation of factors that affect nutrient delivery to the Gulf of Mexico. Parametric time-series models are used to try and separate natural variability in nutrient flux from changes due to other causes. Results indicate that the decrease in annual nutrient fluxes that has occurred between the 1980-1996 baseline period and more recent years can be largely attributed to natural causes (climate and streamflow) and not management actions or other human controlled activities in the Mississippi-Atchafalaya River Basin. The downward trends in total nitrogen, nitrate, ammonium, and orthophosphate that were detected at either the Mississippi River near St. Francisville, La., or the Atchafalaya River at Melville, La., occurred prior to 1995. In spite of the general decrease in nutrient flux, the average size of the Gulf of Mexico hypoxic zone has increased between 1997 and 2007. The reasons for this are not clear but could be due to the type or nature of nutrient delivery. Whereas the annual flux of total nitrogen to the Gulf of Mexico has decreased, the proporti