In March 2002, we conducted 6 shipboard grazing experiments spanning locations from near the largest discharge point of the Mississippi River to a far-field, high salinity location approximately 60 km to the SW. Waters were characterized by salinity, nitrate and size-fractionated chlorophyll a (chl a). None of our stations were in truly oligotrophic conditions typical of the open Gulf of Mexico. Experiments measured growth of 3 phytoplankton size categories (< 5, 5 to 20 and> 20 µm) and associated microzooplankton and mesozoplankton grazing. Rates of phytoplankton growth in all size categories were high in the near-and intermediate-fields, but declined dramatically in the far-field due to nutrient limitation. Microzooplankton grazing rates were low in the near-field, highest in intermediate stations and then declined in the far-field. The mesozooplankton grazing rate was generally low compared to the microzooplankton grazing rate. The mesozooplankton grazing rate was highest at the far-field station where more than 86% of daily growth of> 20 µm phytoplankton was consumed by mesozooplankton. As the plume dispersed and mixed with higher salinity shelf water, inorganic nutrients became exhausted and phytoplankton growth (especially the large diatoms) became nutrient-limited. During this transition, the microzooplankton grazing rate surpassed the phytoplankton growth rate, causing a decline in phytoplankton biomass. Mesozooplankton grazing enhanced this decline by adding an additional grazing mortality, especially to the large phytoplankton cells. The dynamics between growth and grazing mortality in the different size fractions of the phytoplankton community, combined with varying growth rates associated with declining nutrient concentrations, and superimposed on a background of dilution derived from mixing of plume waters with oligotrophic oceanic water, makes interface regions between large rivers and the ocean exceptionally complex.