Net ecosystem CO2 exchange (NEE) is typically measured directly by eddy covariance towers or is estimated by ecosystem process models, yet comparisons between the data obtained by these two methods can show poor correspondence. There are three potential explanations for this discrepancy. First, estimates of NEE as measured by the eddy-covariance technique are laden with uncertainty and can potentially provide a poor baseline for models to be tested against. Second, there could be fundamental problems in model structure that prevent an accurate simulation of NEE. Third, ecosystem process models are dependent on ecophysiological parameter sets derived from field measurements in which a single parameter for a given species can vary considerably. The latter problem suggests that with such broad variation among multiple inputs, any ecosystem modeling scheme must account for the possibility that many combinations of apparently feasible parameter values might not allow the model to emulate the observed NEE dynamics of a terrestrial ecosystem, as well as the possibility that there may be many parameter sets within a particular model structure that can successfully reproduce the observed data. We examined the extent to which these three issues influence estimates of NEE in a widely used ecosystem process model, Biome-BGC, by adapting the generalized likelihood uncertainty estimation (GLUE) methodology. This procedure involved 400,000 model runs, each with randomly generated parameter values from a uniform distribution based on published parameter ranges, resulting in estimates of NEE that were compared to daily NEE data from young and mature Ponderosa pine stands at Metolius, Oregon. Of the 400,000 simulations run with different parameter sets for each age class (800,000 total), over 99% of the simulations underestimated the magnitude of net ecosystem CO2 exchange, with only 4.07% and 0.045% of all simulations providing satisfactory simulations of the field data for the young and mature stands, even when uncertainties in eddy-covariance measurements are accounted for. Results indicate fundamental shortcomings in the ability of this model to produce realistic carbon flux data over the course of forest development, and we suspect that much of the mismatch derives from an inability to realistically model ecosystem respiration. However, difficulties in estimating historic climate data are also a cause for model-data mismatch, particularly in a highly ecotonal region such as central Oregon. This latter difficulty may be less prevalent in other ecosystems, but it nonetheless highlights a challenge in trying to develop a dynamic representation of the terrestrial biosphere. (C) 2009 Elsevier B.V. All rights reserved.