The tendency to worry is a facet of neuroticism that has been shown to mediate the relationship between neuroticism and symptoms of depression and anxiety. The aim of the current study was to investigate the neural correlates of state worry in association with neuroticism. One-hundred twenty participants were selected from an initially recruited sample of 240 women based on their neuroticism score. First, participants completed a questionnaire to assess the excessiveness and uncontrollability of pathological worry. Second, we measured brain activation with functional magnetic resonance imaging (fMRI) while participants were randomly presented with 12 worry-inducing sentences and 12 neutral sentences in a mood induction paradigm. Individuals scoring higher on neuroticism reported to worry more in daily life and to have generated more worry-related thoughts after the presentation of a worry-inducing sentence. Furthermore, imaging results showed the involvement of default mode and emotional brain areas during worry, previously associated with self-related processing and emotion regulation. Specifically, cortical midline structures and the anterior insula showed more activation during worry, when individuals indicated to have generated more worry-related thoughts. Activation in the retrosplenial and visual cortex was decreased in individuals scoring higher on neuroticism during worry, possibly suggesting reduced autobiographical specificity and visual mental imagery. In the literature, both these processes have been related to the cognitive avoidance of emotional distress. Excessive worry features in a number of emotional disorders and results from studies that elucidate its neural basis may help explain how and why neuroticism contributes to vulnerability for psychopathology. Hum Brain Mapp 35:4303-4315, 2014. (C) 2014 Wiley Periodicals, Inc.