The present studies investigate the hypothesis that the locus coeruleus-norepinephrine (LC-NE) system plays a role in the neural substrates underlying individual differences in behavioral reactivity to stress. Individuals were selected from a random sample of Sprague-Dawley rats and categorized as a high responder (HR), middle responder (MR), or low responder (LR) based on the initial locomotor response to a novel open field. Rats with behavioral scores at least 1 SD away from the mean for the subject sample were categorized as HR or LR rats. Middle responder rats exhibited locomotor scores representative of the mean locomotor activity of the population sample. Locomotor activity scores measured 6 days after the initial determination were similar to scores obtained in the original screening, suggesting that the locomotor response to novelty is a stable individual trait. Additionally, locomotor activity during the dark phase of the diurnal cycle was not different among the groups, suggesting that differences in locomotor activity in response to a novel open field are an index of behavioral reactivity to the stressful situation rather than an indicator of global differences in motoric activity. In vivo microdialysis was used to measure extracellular levels of hippocampal NE in the hippocampus. During baseline conditions, the efflux of hippocampal NE was similar among HR, MR, and LR rats. In response to tail-pinch stress, hippocampal NE release was elevated in all groups. This response was significantly greater in HR compared to LR rats. Across all groups, locomotor response in the novel open field was significantly correlated with the magnitude of NE release in response to subsequent application of tail-pinch stress. In contrast, administration of 1.5 mg/kg, i.p., amphetamine resulted in a similar elevation of extracellular NE level among HR, LR, and MR rats. These data suggest that activation of the LC-NE system may be involved in determining the behavioral response of individuals to environmental stress.