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We examined the relationship between stress hormone (cortisol) release and acquisition and consolidation of conditioned fear learning in healthy adults. Participants underwent acquisition of differential fear conditioning, and consolidation was assessed in a 24-h delayed extinction test. The acquisition phase was immediately followed by an 11-min psychosocial stress period (arithmetic test combined with a public speech). Salivary cortisol was sampled at various time points before and after acquisition and retention of fear conditioning. Results showed two effects of endogenous cortisol. Post-acquisition cortisol correlated with fear acquisition in male but not female participants. In addition, post-acquisition cortisol correlated with consolidation of fear but only in those participants with high cortisol levels. We conclude that in the short term, a robust and sexually dimorphic relationship exists between fear learning and stress hormone levels. For those participants whose fear learning is accompanied by high stress hormone levels, a long-term relationship exists between cortisol release and memory consolidation. These short-term and long-term effects may relate to the differential involvement of mineralocorticoid and glucocorticoid receptor subtypes, respectively. The findings have implications for understanding the role of stress, sex, and hormones in different stages of fear learning and memory.Fear conditioning constitutes an adaptive cognitive mechanism in most organisms, allowing them to effectively learn about danger-relevant relationships in the environment and thus enhancing their survival chances. In a typical fear conditioning procedure in the laboratory, a previously neutral conditioned stimulus (CS) predicts the occurrence of an aversive unconditioned stimulus (US) and, as a result, acquires emotional properties. Conditioning is established when the CS triggers a conditioned response in the form of arousal reactions. An increased release of adrenocortical stress hormones-glucocorticoids-through activation of the hypothalamic-pituitary-adrenal (HPA) axis represents an important physiologic component of such arousal responses to fearful stimuli. The principal glucocorticoid in humans is cortisol.Basal and stress levels of glucocorticoids vary across individuals (Piazza et al. 1991;Meaney et al. 1993;Cools and Gingras 1998;Kirschbaum et al. 1999;Kabbaj et al. 2000;Stone et al. 2001;Bartels et al. 2003;Rohleder et al. 2003;Steptoe et al. 2003) and play an important but complex role in learning and memory (McEwen and Sapolsky 1995;Roozendaal 2003;Wolf 2003). While cortisol may be detrimental to memory function under some circumstances-i.e., when levels are elevated chronically (Starkman et al. 1992;Luine et al. 1993Luine et al. , 1994Arbel et al. 1994;Bodnoff et al. 1995;Conrad et al. 1996;Newcomer et al. 1999;Park et al. 2001) or during memory retrieval (De Quervain et al. 1998Buss et al. 2004)-they also have acute facilitative effects, presumably constituting part of the underlying neurobiological m...