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Land use and other human disturbances have significant impacts on physicochemical and biological conditions of stream systems. A good understanding of the relationships among those factors will help aquatic resource managers to make wise decisions in protecting un-impacted systems and rehabilitate degraded systems. The objectives of this study were to employ watershed model results to obtain in-stream flow and water quality data and fill a critical gap in data collection. This data was then used to describe and estimate fish index of biological integrity (IBI) and the percent of intolerant fish individuals representing ecological health at un-sampled stream reaches within the Saginaw Bay basin. Three methods were used in connecting in-stream variables to fish measures including stepwise linear regression, partial least squares regression, and fuzzy logic. The model developed using fuzzy logic showed the best performance based on the highest R2 for IBI (R2 = 0.48) and for percent intolerant fish individuals (R2 = 0.21) and the lowest mean square error for IBI (MSE=268) and for percent intolerant fish (MSE=275). Overall, average annual flow rate had the strongest influence on IBI, whereas nutrient concentration (average annual organic phosphorus) showed the largest influence on the percentage of intolerant individuals. Based on the best model identified from the previous section, predictions were made for pre-settlement landuse and climate conditions. Results showed overall significantly higher IBI and percent intolerant individuals under pre-settlement landuse scenario. This implies that landuse change from pre-settlement to current has profound negative impacts on stream health within the study area. Our results also showed that including pre-settlement climate factors in our models is ultimately important because climate factors have strong influences on stream flow and water quality measures that interactively affect stream health as indicated by fish measures. These results suggest that efforts to model historic baseline habitat conditions and to provide context for stream health assessments should include both pre-settlement land use and climate conditions.