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Abstract: The weekend ozone effect refers to changes in ground-level ozone concentrations on weekends resulting from anthropogenic emission changes from weekdays and weekends. This study applied a three-dimensional photochemical grid model for a three-month summer period to examine the weekend ozone effect in the Midwestern US (the north-central and north-eastern part of US) at both urban and regional scales. The model generally reproduced the observed daily maximum 1-h and 8-h ozone and also correctly predicted weekend changes in the VOC-to-NO x ratio. So-called dynamic evaluation of the modeled weekend ozone changes throughout the summer revealed that meteorology had a bigger impact on the summer 2005 weekend ozone effect than anthropogenic emission changes partly because meteorology strongly influences biogenic emissions. To avoid the confounding effect of meteorological changes, weekend ozone differences were determined by using a second simulation modeled with weekday emissions for all days of week. Ozone differences between the base case and the second simulation isolated the effect of weekday/weekend emission changes. To further distinguish local effects of weekend emission changes from transported regional ozone differences, a third simulation applied weekend emission changes only within two urban areas with all weekday emissions for the remaining areas. The ozone differences between the base case and the third simulations revealed that the effect of regional weekend emission differences is projected to be mostly lowered ozone on weekends. On the other hand, the difference between the second and third simulations revealed that weekend emission changes in two urban areas increased ozone locally in the urban centers and immediately downwind areas but lowered ozone further downwind. The sign-change in the weekend ozone effect from urban centers to downwind areas is explained by a matching change in sign of ozone sensitivity to NO x emissions which was confirmed by computing ozone sensitivities to domain-wide NO x and VOC emissions. The sensitivity analysis also showed that weekday/weekend ozone differences in the Midwestern US are due primarily to weekend reductions in NO x emissions. [Copyright &y& Elsevier]