It is customary that growers apply high doses of nutrients to the soil in order to achieve high yields, with detrimental consequences for the environment; but no information exists with regards to the crop response to high fertilization levels. To evaluate the physiological response of lettuce (Lactuca sativa L.) to various root zone nutrient concentrations (expressed as electrical conductivity, from 0.6 to 10 dS m-1), a replicated experiment was conducted using increasing concentrations of macronutrients applied to the root zone in an aeroponic system. Leaf photosynthesis and chlorophyll fluorescence were measured using a portable infrared gas analyzer attached with a fluorometer. Leaf nutrient content was analyzed by mass spectrometry and NO3-N was determined by flow injection analysis. Leaf photosynthetic rates increased when the solution concentration was raised from 0.6 to 4.8 dS m-1, but further increases in solution concentration did not result in any differences. The enhancement in photosynthetic rates was related to higher concentrations of N, P, Mg, and S in leaves. Leaf K content was correlated with stomatal conductance. Maximum growth was achieved with solution concentrations between 1.2 and 4.8 dS m-1 while at 10.0 dS m-1 leaf production was reduced by 30%. It is concluded that at high concentration of nutrients supplied in the root zone, yield reduces because of a combination of decreased stomatal conductance and leaf area.