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Simulation models are widely used to assess water contamination risk associated with pesticide use and for evaluating effectiveness of agricultural conservation practices. Currently, the APEX (Agricultural Policy/Environmental eXtender) model is being used for this purpose in the USDA Conservation Effects Assessment Project (CEAP) Cropland National Assessment. In support of the CEAP modeling effort, APEX was calibrated and validated using a nine-year record (1999-2007) of crop yield, surface runoff, and tile outflow and an eight-year record (1999-2006) of soluble pendimethalin and fluometuron herbicide losses from fields in a cotton-peanut rotation located in the Atlantic Coastal Plain region of south-central Georgia. Conventional tillage and strip tillage were directly compared. Monthly surface runoff was calibrated by adjusting three variables: curve number index coefficient (CNIC), a driver of the USDA Natural Resources Conservation Service (NRCS) runoff curve number; runoff curve number for the average soil moisture condition 2 (CN2); and irrigation runoff ratio (IRR). Statistical performance criteria for monthly and annual results were r2 > 0.5, NSE > 0.45, and PBIAS < 20%, based on prior modeling studies. Monthly runoff statistics showed r2 values of 0.62 to 0.82 and met satisfactory criteria between observed and simulated surface runoff for both tillage types, with Nash-Sutcliffe efficiency (NSE) values of 0.62 to 0.80 and PBIAS values within 19% during the calibration and validation periods. Monthly subsurface lateral flow performance statistics for the strip-tilled plots were satisfactory during the calibration period but weak for the conventional tillage plots. Monthly performance statistics for fluometuron runoff for the conventional tillage plots were below satisfactory criteria. Other monthly statistics for fluometuron and pendimethalin losses were weak. Measured and predicted crop yield and annual runoff for both tillage systems were well aligned and met satisfactory statistical criteria. APEX performance was satisfactory for annual fluometuron soluble runoff for the conventionally tilled plots but not satisfactory for the strip-tilled plot with less runoff. The models performance was unsatisfactory for annual subsurface lateral flow and fluometuron transport in subsurface lateral flow for both tillage systems. The percent bias statistical parameter (PBIAS) was within 20% for all annual mean correlations, indicating that APEX effectively replicated annual means for crop yield, runoff, subsurface lateral flow, and pesticide losses. Measured and simulated results of conservation tillage effects were in close agreement for decreased water and pesticide runoff as well as increased subsurface lateral flow and associated fluometuron losses. Although fluometuron losses in subsurface lateral flow approximately doubled with conservation tillage, loading was still small compared to fluometuron in runoff from the conventionally tilled plots. Results demonstrate APEXs strength in simulating runoff in this landscape, but less satisfactory results were obtained for pendimethalin runoff, subsurface lateral flow, and fluometuron losses in subsurface lateral flow.