As a result of fish kills in the Neuse River estuary in 1995, nutrient reduction strategies were developed for point and nonpoint sources in the basin. However, because of the interannual variability in the natural system and the resulting complex hydrologic-nutrient inter- actions, it is difficult to detect through a short-term observational program the effects of management activities on Neuse River estuary water quality and aquatic health. A properly constructed water-quality model can be used to evaluate some of the potential effects of manage- ment actions on estuarine water quality. Such a model can be used to predict estuarine response to present and proposed nutrient strategies under the same set of meteorological and hydrologic conditions, thus removing the vagaries of weather and streamflow from the analysis. A two-dimensional, laterally averaged hydrodynamic and water-quality modeling framework was developed for the Neuse River estuary by using previously collected data. Development of the modeling framework consisted of (1) computational grid development, (2) assembly of data for model boundary conditions and model testing, (3) selection of initial values of model parameters, and (4) limited model testing. The model domain extends from Streets Ferry to Oriental, N.C., includes seven lateral embayments that have continual exchange with the main- stem of the estuary, three point-source discharges, and three tributary streams. Thirty-five computational segments represent the mainstem of the estuary, and the entire framework contains a total of 60 computa- tional segments. Each computational cell is 0.5 meter thick; segment lengths range from 500 meters to 7,125 meters. Data that were used to develop the modeling framework were collected during March through October 1991 and represent the most comprehensive data set available prior to 1997. Most of the data were collected by the North Carolina Division of Water Quality, the University of North Carolina Institute of Marine Sciences, and the U.S. Geological Survey. Limitations in the modeling framework were clearly identified. These limitations formed the basis for a set of suggestions to refine the Neuse River estuary water-quality model.