A lack of adequate experimental models of emotional reactions to aversive stimuli is an impediment to furthering our understanding of the psychopharmacology of fear and anxiety in humans. Finding procedures that enable us to test putative anxiety-relieving agents would greatly facilitate this type of research. The startle reflex is an ideal tool for such an endeavor. The so-called fear-potentiated startle reflex (FPS) has clear face validity, well-defined neuronal system, and cross-species generalization. In addition, in rodents the fear-potentiated startle reflex effect is blocked or reduced by drugs that are anxiolytic in humans. However, the few psychopharmacological studies conducted so far in humans have yielded inconsistent results. One possibility is that prior studies have not employed optimal designs to test the effects of anxiolytics. Our previous studies in anxious individuals and patients with anxiety disorders, as well as animal studies, suggest that the potentiation of startle by aversive states can be mediated by two distinct psychological and neurobiological mechanisms. One mediates the short-term potentiation of startle to explicit threatening cues, and the other the long-term potentiation of startle by contextual cues. We have shown that the benzodiazepines alprazolam act preferentially on FPS to contextual cues. The objectives of the following studies are to further test the psychopharmacological validity of the model using recognized anxiolytics (the SSRI citalopram), to test the anxiolytic properties of compounds that are hypothesized to be anxiolytic (the angiotensin receptor blocker candesartan) based on pre-clinical data, and to examine the role of cortisol in startle potentiation.