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Instruction is a highly efficient means to teach new behavioral rules.Despite its relevance for education, factors altering instruction efficacy are unknown.Acute stress boosts the beneficial effect of an instruction on stimulus-response learning.This enhancement was correlated with the individual cortisol and blood pressure response to stress.High trait anxiety reduces the benefit of an instruction on learning.Learning by explicit instruction is a highly efficient way to instantaneously learn new behaviors and to overcome potentially harmful learning by trial-and-error. Despite the importance of instructed learning for education, influences on the efficacy of an instruction are currently unknown. Decades of research, however, showed that stress is a powerful modulator of learning and memory, including the acquisition of stimulus-response (S-R) associations. Moreover, brain areas critical for instructed learning are a major target of hormones and neurotransmitters released during stress. Thus, we investigated here whether acute stress affects instructed S-R learning and whether this effect differs for trial-and-error learning. To this end, healthy participants underwent a stressor (Socially Evaluated Cold Pressor Test) or a control manipulation before learning arbitrary S-R associations. For half of the stimuli, participants were explicitly instructed about the correct association, whereas the remaining associations had to be learned by trial-and-error. As expected, the instruction resulted in better performance and enhanced explicit rule knowledge compared to trial-and-error learning. Stress further boosted the beneficial effect of an explicit instruction on learning performance, while leaving trial-and-error learning unchanged. These beneficial effects of stress were directly correlated with the activity of the autonomic nervous system and the concentration of cortisol. Moreover, acute stress could override the detrimental effect of high trait anxiety levels on instructed S-R learning performance. Our findings indicate that acute stress may facilitate learning from instruction, which may represent a highly efficient way to learn how to act, without the necessity of own experience, that helps to save cognitive resources during a stressful encounter.