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Nutrient enrichment and eutrophication of estuarine and coastal waters are accelerating, and there is a need to develop rapidly detectable and quantifiable indicators of these changes. Coastal systems are also impacted by climatic perturbations, including droughts, storms, and floods, the frequencies of which may be increasing. Phytoplankton are excellent indicators of ecological change. They are relatively easy to detect, identify, and quantify; they conduct a large share of primary production; and they are sensitive to diverse environmental stressors. In this study, phytoplankton total biomass, as chlorophyll a, and group-specific chemotaxonomic indicators (including chlorophylls and carotenoids) were used to characterize community responses to human (nutrient) and climatic (hydrologic) perturbations in the Neuse River Estuary-Pamlico Sound, North Carolina, USA. This estuarine-coastal continuum is experiencing anthropogenic nutrient enrichment and, since 1996, a rise in hurricane frequency. Freshwater input and flushing strongly interacted with supplies of the limiting nutrient nitrogen (N) to determine the location, magnitude, and composition of phytoplankton biomass along this continuum. Elevated flow (high flushing) following hurricanes favored dominance by the fast-growing chlorophytes and cryptophytes. Diatoms tended to dominate under moderate flow, while dinoflagellates and cyanobacteria increased in dominance when low flow prevailed in winter/spring and summer/fall, respectively. Depending on seasonal hydrologic cycles and episodic (hurricane) conditions, phytoplankton community structure differed substantially. These changes impact eutrophi- cation, food web, biogeochemical (e.g., hypoxia), and habitat conditions in this and other coastal ecosystems currently experiencing changes in nutrient inputs and climatic events. Phytoplankton-based indicators are adaptable to unattended monitoring platforms (e.g., ferries) that can be coupled to remote sensing and modeling efforts, in order to evaluate and help manage ecological change at ecosystem and regional scales.