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Background The classic conception of stress involves undifferentiated negative affect and corresponding biological reactivity. The present study hypothesized a new conception, disaggregating stress into emotion-specific, contrasting patterns of biological response. Specifically, it hypothesized contrasting patterns for indignation (comprised of anger and disgust) versus fear. Moreover, it hypothesized that facial expressions of these emotions would signal corresponding biological stress responses. Methods Ninety-two adults engaged in annoyingly difficult stress-challenge tasks, during which cardiovascular responses, hypothalamic-pituitary-adrenocortical (HPA) axis responses (i.e., cortisol), emotional expressions (i.e., facial muscle movements), and subjective emotional experience were assessed. Results Pronounced individual differences emerged in specific emotional responses to the stressors. Analyses of facial expressions revealed that the more fear individuals displayed in response to the stressors, the higher their cardiovascular and cortisol responses to stress. By contrast, the more indignation individuals displayed in response to the same stressors the lower their cortisol levels and cardiovascular responses. Conclusions Facial expressions of emotion signal biological responses to stress. Fear expressions signal elevated cortisol and cardiovascular reactivity; indignation signals attenuated cortisol and cardiovascular reactivity, patterns that implicate individual differences in stress appraisals. Rather than conceptualizing stress as generalized negative affect, studies can be informed by this emotion-specific approach to stress responses.