Increasing the diversity in the sites of action of herbicides is an important method for delaying and preventing herbicide resistance in weed populations. Benzoylprop-ethyl, a lipid biosynthesis inhibitor, is used to increase the diversity of herbicide sites of action and control ACCase- and ALS-resistant Avena sterilis subsp. ludoviciana (Durieu.) Gillet & Magne) populations in Iran. Drought stress, especially in arid and semiarid areas, affects weed physiology and performance of herbicides. Accordingly, a series of dose-response assays was conducted to evaluate the efficacy of benzoylprop-ethyl under drought-(60% Field Capacity) and non-drought-stress (90% Field Capacity) conditions on A. sterilis subsp. ludoviciana. Also, some biochemical and physiological traits of A. sterilis subsp. ludoviciana including leaf chlorophyll content, leaf greenness index, photosynthesis rate and stomatal conductance were investigated under the drought and non-drought regimes. The efficacy of benzoylpmp-ethyl decreased significantly under drought condition. The effective dose reducing dry weight by 90% in relation to the untreated control (i.e., ED90) for the drought-stressed plants was significantly (P <0.01) higher than that of the non-drought-stressed plants, where it was 895 (+/- 112.6) and 1543 (+/- 205.3) g a.i. ha(-1), respectively. The drought index (the ratio of the ED90 at 60% FC relative to ED(90 )at 90% FC) was 1.68 (+/- 0.16) and thus, significantly higher than 1. Leaf chlorophyll content (chl a and chl b) and leaf greenness index increased under drought conditions, while the photosynthesis rate, stomatal conductance, and the chl a/b decreased. The efficacy reduction of benzoylpmp-ethyl on drought-stressed plants might be due to photosynthesis reduction and reduced stomatal conductance leading to reduced herbicide uptake. Tracking local weather forecasts, monitoring water soil content and irrigating the field before herbicide application were suggested to overcome the detrimental effect of drought stress on the efficacy of benzoylprop-ethyl. Potential tactics such as using adjuvants, different formulations and early application timing of benzoylprop-ethyl to tackle the problem were proposed for future studies.