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Inmanyplant species, long-term exposure to elevatedCO2 concentration results in a reduction in photosynthetic capacity, known as acclimation. This process is mainly explained by a feedback inhibition mechanism. The supply of a fraction of the nitrogen (N) in the nutrient solution as NH4+ can play an important role in the maintenance of photosynthetic activity and could mitigate the acclimation process. The aims of the present work were to study the photosynthetic response of sweet pepper (Capsicum annuum L.) to CO2 enrichment in Mediterranean greenhouse conditions, throughout the crop growth cycle and to evaluate the supply of NH4+ in the nutrient solution as a strategy to enhance the long-term response to CO2 at different levels of salinity. The experiment was conducted in two identical greenhouses: one with CO2 enrichment according to the ventilation, maintaining a high concentration when the vents were closed and a near-atmospheric level when the vents were open and one without. Sweet pepper plants were grown in both greenhouses, being irrigated with two levels of water salinity and two N sources: (i) NO3- and (ii) NO3- plus NH4+. A reduction in the response of photosynthesis to high CO2 concentration was found in the enriched plants after 135 days ofCO2 supply, with respect to the reference plants. The leaf photosynthesis rate measured at high CO2 concentration showed a closer relationship with the leaf N concentration than the non-structural carbohydrate concentration. The relative yield gain of the CO2-enriched plants progressively decreased after reaching a maximum value; this was probably associated with the photosynthetic acclimation process. This decrease was delayed by the use ofNH4+ in the nutrient solution at low salinity. Knowledge of the crop phase when acclimation to high CO2 concentration occurs can be the basis for deciding when to impose an early cessation of CO2 application, as a strategy to improve the economic efficiency of CO2 supply in Mediterranean conditions. [ABSTRACT FROM AUTHOR]