The Mississippi River carries very high concentrations of nutrients into the otherwise oligotrophic Gulf of Mexico, resulting in high primary production and hypoxia along the Louisiana continental shelf. The hypothesis that nitrogen availability controls and ultimately limits phytoplankton production on the shelf was tested by measuring an indicator of nitrogen deficiency, the ratio of intracellular free amino acids/particulate protein (AA/Pr), in the area of the Mississippi River plume on a spring and a summer cruise. Neither AA/Pr ratios or nutrients in the water showed nitrogen limitation to be widespread. Ammonium concentrations were generally quite high, so the lack of phytoplankton nitrogen deficiency can be explained by rapid regeneration rates. Nitrogen limitation was most likely in the summer at high salinities. However, ratios of dissolved nutrient concentrations suggested that silicate was as likely, or sometimes more likely, to be a limiting nutrient than nitrogen. Although silicate depletion may not cause a decrease in productivity, it could result in major changes in phytoplankton size and species composition, and ultimately influence trophodynamics, regeneration, the fate of carbon, and severity and extent of hypoxia.