Increased delivery of biologically available nitrogen to estuaries and coastal oceans in recent decades has been linked to eutrophication and seasonal hypoxia in the northern Gulf of Mexico and elsewhere. We have developed a model that accounts for 95% of annual variation in delivery of nitrate to the Gulf of Mexico by the Mississippi River in 1960-98. Retrospective analysis indicates that this nitrate flux could have been reduced by 33% if the use of nitrogen-containing fertilizer in the Mississippi River basin had been cut by 12%.