Background: A vital component of an organism's response to acute stress is a surge in vigilance that serves to optimize the detection and assessment of threats to its homeostasis. The amygdala is thought to regulate this process, but in humans, acute stress and amygdala function have up to now only been studied in isolation. Hence, we developed an integrated design using functional magnetic resonance imaging to investigate the immediate effects of controlled stress induction on amygdala function. Methods: In 27 healthy female participants, we studied brain responses to emotional facial stimuli, embedded in an either acutely stressful or neutral context by means of adjoining movie clips. Results: A variety of physiological and psychological measures confirmed successful induction of moderate levels of acute stress. More importantly, this context manipulation shifted the amygdala toward higher sensitivity as well as lower specificity, that is, stress induction augmented amygdala responses to equally high levels for threat-related and positively valenced stimuli, thereby diminishing a threat-selective response pattern. Additionally, stress amplified sensory processing in early visual regions and the face responsive area of the fusiform gyrus but not in a frontal region involved in task execution. Conclusions: A shift of amygdala function toward heightened sensitivity with lower levels of specificity suggests a state of indiscriminate hypervigilance under stress. Although this represents initial survival value in adverse situations where the risk for false negatives in the detection of potential threats should be minimized, it might similarly play a causative role in the sequelae of traumatic events. © 2009 Society of Biological Psychiatry.